WorldWideScience

Sample records for advanced pancreatic cancer

  1. Controlled clinical study on pancreatic stenting in the relief of pain of advanced pancreatic cancer with dilated pancreatic duct

    Institute of Scientific and Technical Information of China (English)

    高飞

    2014-01-01

    Objective To explore the efficacy of pancreatic stenting in the relief of abdominal pain of advanced pancreatic cancer with dilated pancreatic duct.Methods A tolal of 61 patients with advanced pancreatic carcinoma companied with dilated pancreatic duct were divided into two groups.Twenty-eight cases(two cases were excluded because of stent loss)in stent group treated with

  2. Biologic therapies for advanced pancreatic cancer.

    Science.gov (United States)

    He, Aiwu Ruth; Lindenberg, Andreas Peter; Marshall, John Lindsay

    2008-08-01

    Patients with metastatic pancreatic cancer have poor prognosis and short survival due to lack of effective therapy and aggressiveness of the disease. Pancreatic cancer has widespread chromosomal instability, including a high rate of translocations and deletions. Upregulated EGF signaling and mutation of K-RAS are found in most pancreatic cancers. Therefore, inhibitors that target EGF receptor, K-RAS, RAF, MEK, mTOR, VEGF and PDGF, for example, have been evaluated in patients with pancreatic cancer. Although significant activities of these inhibitors have not been observed in the majority of pancreatic cancer patients, an enormous amount of experience and knowledge has been obtained from recent clinical trials. With a better inhibitor or combination of inhibitors, and improvement in the selection of patients for available inhibitors, better therapy for pancreatic cancer is on the horizon.

  3. Advances in early diagnosis and therapy of pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    Qiang Xu; Tai-Ping Zhang; Yu-Pei Zhao

    2011-01-01

    BACKGROUND: Pancreatic cancer remains a devastating disease with a 5-year survival rate of less than 5%. Recent advances in diagnostic methods and therapeutic approaches have increased the possibility of improving the existing poor prognosis. DATA  SOURCES: English-language articles reporting early diagnosis and therapy of pancreatic cancer were searched from the MEDLINE and PubMed databases, Chinese-language articleswerefromCHKD(ChinaHospitalKnowledgeDatabase). RESULT: The current literature about pancreatic cancer was reviewed from three aspects: statistics, screening and early detection, and therapy. CONCLUSIONS: Early detection and screening of pancreatic cancer currently should be limited to high risk patients. Surgical resection is the only curative approach available, with some recent improvement in outcomes. Gemcitabine has been a standard treatment during the last decade. Gemcitabine-based combination treatment, especially combined with newer molecular targeted agents, is promising. The rationale for radiotherapy is controversial, but with the recent development of modern radiation delivery techniques, radiotherapy should be intensified. Patients with borderline pancreatic cancer could benefit from neoadjuvant therapy but more evidence is needed and the best neoadjuvant regimen is still to be determined.

  4. Photodynamic therapy for locally advanced pancreatic cancer: early clinical results

    Science.gov (United States)

    Sandanayake, N. S.; Huggett, M. T.; Bown, S. G.; Pogue, B. W.; Hasan, T.; Pereira, S. P.

    2010-02-01

    Pancreatic adenocarcinoma ranks as the fourth most common cause of cancer death in the USA. Patients usually present late with advanced disease, limiting attempted curative surgery to 10% of cases. Overall prognosis is poor with one-year survival rates of less than 10% with palliative chemotherapy and/or radiotherapy. Given these dismal results, a minimally invasive treatment capable of local destruction of tumor tissue with low morbidity may have a place in the treatment of this disease. In this paper we review the preclinical photodynamic therapy (PDT) studies which have shown that it is possible to achieve a zone of necrosis in normal pancreas and implanted tumour tissue. Side effects of treatment and evidence of a potential survival advantage are discussed. We describe the only published clinical study of pancreatic interstitial PDT, which was carried out by our group (Bown et al Gut 2002), in 16 patients with unresectable locally advanced pancreatic adenocarcinoma. All patients had evidence of tumor necrosis on follow-up imaging, with a median survival from diagnosis of 12.5 months. Finally, we outline a phase I dose-escalation study of verteporfin single fibre PDT followed by standard gemcitabine chemotherapy which our group is currently undertaking in patients with locally advanced pancreatic cancer. Randomized controlled studies are also planned.

  5. Definitive concurrent chemoradiotherapy in locally advanced pancreatic cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kwak, Yoo Kang; Lee, Jong Hoon; Lee, Myung Ah; Chun, Hoo Geun; Kim, Dong Goo; You, Young Kyoung; Hong, Tae Ho; Jang, Hong Seok [Seoul St. Mary' s Hospital, The Catholic University of Korea College of Medicine, Seoul (Korea, Republic of)

    2014-06-15

    Survival outcome of locally advanced pancreatic cancer has been poor and little is known about prognostic factors of the disease, especially in locally advanced cases treated with concurrent chemoradiation. This study was to analyze overall survival and prognostic factors of patients treated with concurrent chemoradiotherapy (CCRT) in locally advanced pancreatic cancer. Medical records of 34 patients diagnosed with unresectable pancreatic cancer and treated with definitive CCRT, from December 2003 to December 2012, were reviewed. Median prescribed radiation dose was 50.4 Gy (range, 41.4 to 55.8 Gy), once daily, five times per week, 1.8 to 3 Gy per fraction. With a mean follow-up of 10 months (range, 0 to 49 months), median overall survival was 9 months. The 1- and 2-year survival rates were 40% and 10%, respectively. Median and mean time to progression were 5 and 7 months, respectively. Prognostic parameters related to overall survival were post-CCRT CA19-9 (p = 0.02), the Eastern Cooperative Oncology Group (ECOG) status (p < 0.01), and radiation dose (p = 0.04) according to univariate analysis. In multivariate analysis, post-CCRT CA19-9 value below 180 U/mL and ECOG status 0 or 1 were statistically significant independent prognostic factors associated with improved overall survival (p < 0.01 and p = 0.02, respectively). Overall treatment results in locally advanced pancreatic cancer are relatively poor and few improvements have been accomplished in the past decades. Post-treatment CA19-9 below 180 U/mL and ECOG performance status 0 and 1 were significantly associated with an improved overall survival.

  6. Gemcitabine in elderly patients with advanced pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    Olivia Hentic; Chantal Dreyer; Vinciane Rebours; Magaly Zappa; Philippe Lévy; Eric Raymond; Philippe Ruszniewski; Pascal Hammel

    2011-01-01

    AIM: To assess feasibility, tolerability and efficacy of gemcitabine-based chemotherapy in patients ≥ 75 years old with advanced pancreatic cancer. METHODS: All consecutive patients ≥ 75 years old with advanced pancreatic adenocarcinoma were included in this retrospective study. Necessary criteria to receive chemotherapy were: performance status 0-2, adequate biological parameters and no serious comorbidities. Other patients received best supportive care (BSC). RESULTS: Thirty-eight patients (53% women, median age 78 years, range 75-84) with pancreatic cancer (metastatic: n = 20, locally advanced: n = 18) were studied. Among them, 30 (79%) were able to receive chemotherapy [median number: 9 infusions (1-45)]. Six patients (23%) had at least one episode of grade 3 neutropenia and one patient developed a grade 3 hemolytic-uremic syndrome. No toxic death occurred. Three patients (11%) had a partial tumor response, 13 (46%) had a stable disease and 12 (43%) had a tumor progression. Median survival was 9.1 mo (metastatic: 6.9 mo, locally advanced: 11.4 mo). CONCLUSION: Tolerance and efficacy of gemcitabinebased chemotherapy is acceptable in elderly patients in good condition, with similar results to younger patients.

  7. Pancreatic Cancer

    Science.gov (United States)

    ... hormones that help control blood sugar levels. Pancreatic cancer usually begins in the cells that produce the juices. Some risk factors for developing pancreatic cancer include Smoking Long-term diabetes Chronic pancreatitis Certain ...

  8. Chemotherapy Regimen Extends Survival in Advanced Pancreatic Cancer Patients

    Science.gov (United States)

    A four-drug chemotherapy regimen has produced the longest improvement in survival ever seen in a phase III clinical trial of patients with metastatic pancreatic cancer, one of the deadliest types of cancer.

  9. Is it relevant that intra-arterial chemotherapy may be effective for advanced pancreatic cancer?

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Unresectable pancreatic cancers have an extremely dismal prognosis and chemoresistant nature. The treatment of pancreatic cancer is still problematic.Gemcitabine is a promising new agent that has been studied recently for palliation of advanced pancreatic cancer. However, the response rates have been highly variable, and are often irreproducible. To improve this low response rate, various treatments are needed because no standard treatment exists. Intra-arterial chemotherapy is considered to take advantage of the first pass effect of the drug, generating higher local drug concentrations in tumor cells with lower toxicity.Regional intra-arterial chemotherapy may provide high levels of cytostatic concentrations within the tumor and, simultaneously, a low rate of systemic side effects compared with systemic administration of anti-neoplastic drugs. Intra-arterial chemotherapy has been introduced as an alternative treatment for advanced pancreatic cancer. Further clinical trials of this method should be subjected to a prospective randomized controlled study for advanced pancreatic cancer.

  10. Long-term results of concurrent radiotherapy and UFT in patients with locally advanced pancreatic cancer

    DEFF Research Database (Denmark)

    Bjerregaard, Jon K; Mortensen, Michael B; Jensen, Helle A;

    2009-01-01

    BACKGROUND: Definition and treatment options for locally advanced non-resectable pancreatic cancer (LAPC) vary. Treatment options range from palliative chemotherapy to chemoradiotherapy (CRT). Several studies have shown that a number of patients become resectable after complementary treatment prior...

  11. Advances in understanding the molecular mechanism of pancreatic cancer metastasis

    Institute of Scientific and Technical Information of China (English)

    Yong-Xing Du; Zi-Wen Liu; Lei You; Wen-Ming Wu; Yu-Pei Zhao

    2016-01-01

    BACKGROUND: Pancreatic cancer (PC) is usually diagnosed at the late-stage and therefore, has widespread metastasis and a very high mortality rate. The mechanisms underlying PC metastasis are not well understood. Recent advances in genomic sequencing have identiifed groups of gene mutations that affect PC metastasis, but studies elucidating their roles are lacking. The present review was to investigate the molecu-lar mechanisms of PC metastasis. DATA SOURCES: Relevant articles on PC metastasis were searched in MEDLINE via PubMed prior to April 2015. The search was limited in English publications. RESULTS: PC metastatic cascades are multi-factorial events including both intrinsic and extrinsic elements. This review highlights the most important genetic alterations and other mechanisms that account for PC invasion and metastasis, with particular regard to epithelial-mesenchymal transition, inlfammation, stress response, and circulating tumor cells. CONCLUSIONS: Analyses of relevant gene functions and signaling pathways are needed to establish the gene regula-tory network and to deifne the pivotal modulators. Another promising area of study is the genotyping and phenotyping of circulating tumor cells, which could lead to a new era of per-sonalized therapy by identifying speciifc markers and targets.

  12. Recent advances in the surgical treatment of pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    A Shankar; RCG Russell

    2001-01-01

    @@ INTRODUCTION Pancreatic cancer remains the fourth commonest cause of cancer related death in the western world[1]. The prognosis remains dismal due partly to late presentation, with associated low resectability rates, and the aggressive biological nature of these tumors. The median survival time from diagnosis in unresectable tumors remains only 4 6 months.For those patients amenable to surgical resection over the last 20 years have seen marked improvements in postoperative mortality and morbidity, especially in specialist pancreatic centres 23. Despite these changes long-term survival remains low. with a total 5-year survival rate remaining less than 5%.Patients with ampullary cancer have a better 5-year survival of 40°%-60°%.

  13. The Efficacy of High-Intensity Focused Ultrasound (HIFU) in Advanced Pancreatic Cancer

    Institute of Scientific and Technical Information of China (English)

    Bo Xie; Jiajun Ling; Weiming Zhang; Xueqin Huang; Jihua Zhen; Yanzhe Huang

    2008-01-01

    OBJECTIVE To observe the efficacy of high-intensity focused ultrasound (HIFU)in the treatment of late-stage pancreatic cancer.METHODS Sixteen patients with advanced pancreatic cancer received HIFU therapy.Evaluation of efficacy was made on the basis of changes in clinical symptoms and variations in the tumor echo and size.RESULTS Clinical symptoms such as pain were significantly alleviated,echo of the tumor was enhanced with B-US and the quality of life such as eating,sleeping and mental status was markedly improved;no serious complications were observed.CONCLUSION The use of HIFU in the treatment of advanced pancreatic cancer is feasible and safe.It is effective in killing the carcinoma cells and alleviaring pain.This technique may offer non-invasive therapy for the treatment of patients with late-stage pancreatic cancer.

  14. L-Carnitine-supplementation in advanced pancreatic cancer (CARPAN) - a randomized multicentre trial

    OpenAIRE

    Kraft Matthias; Kraft Kathleen; Gärtner Simone; Mayerle Julia; Simon Peter; Weber Eckhard; Schütte Kerstin; Stieler Jens; Koula-Jenik Heide; Holzhauer Peter; Gröber Uwe; Engel Georg; Müller Cornelia; Feng You-Shan; Aghdassi Ali

    2012-01-01

    Abstract Background Cachexia, a >10% loss of body-weight, is one factor determining the poor prognosis of pancreatic cancer. Deficiency of L-Carnitine has been proposed to cause cancer cachexia. Findings We screened 152 and enrolled 72 patients suffering from advanced pancreatic cancer in a prospective, multi-centre, placebo-controlled, randomized and double-blinded trial to receive oral L-Carnitine (4 g) or placebo for 12 weeks. At entry patients reported a mean weight loss of 12 ± 2,5 (SEM)...

  15. Pancreatic Cancer: A Review.

    Science.gov (United States)

    Yabar, Cinthya S; Winter, Jordan M

    2016-09-01

    Pancreatic cancer is now the third leading cause of cancer related deaths in the United States, yet advances in treatment options have been minimal over the past decade. In this review, we summarize the evaluation and treatments for this disease. We highlight molecular advances that hopefully will soon translate into improved outcomes.

  16. Surgery for Pancreatic Cancer

    Science.gov (United States)

    ... of the Tumor Pancreatic Cancer Treating Pancreatic Cancer Surgery for Pancreatic Cancer Two general types of surgery ... how far the cancer has spread. Potentially curative surgery Studies have shown that removing only part of ...

  17. Pancreatic Cancer Early Detection Program

    Science.gov (United States)

    2014-07-30

    Pancreatic Cancer; Pancreas Cancer; Pancreatic Adenocarcinoma; Familial Pancreatic Cancer; BRCA 1/2; HNPCC; Lynch Syndrome; Hereditary Pancreatitis; FAMMM; Familial Atypical Multiple Mole Melanoma; Peutz Jeghers Syndrome

  18. Technical advances in endoscopic ultrasound-guided fiducial placement for the treatment of pancreatic cancer

    NARCIS (Netherlands)

    Chavalitdhamrong, D.; DiMaio, C.J.; Siersema, P.D.; Wagh, M.S.

    2015-01-01

    Radiation therapy has an important role in the treatment of locally advanced or metastatic pancreatic cancer and can be used alone or in conjunction with surgery and/or systemic chemotherapy. Because of the challenge of delivering an accurate and optimal radiation dose, image-guided radiation therap

  19. Analgesic effect of high intensity focused ultrasound in patients with advanced pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    Xinjin Tan; Jian Chen; Li Ren; Ruilu Lin; Zailian Chen

    2013-01-01

    Objective:The aim of this study was to evaluate the analgesic ef ect of high intensity focused ultrasound (HIFU) in patients with advanced pancreatic cancer. Methods:A total of 106 patients with advanced pancreatic cancer accompanied by abdominal pain were treated by HIFU. Pain intensities and quantities of morphine consumption before and after treatment were observed and compared. Results:The average pain intensities before treatment, and at d3, d7 after treatment were 5.80 ± 2.14, 2.73 ± 2.68, 2.45 ± 2.43 respectively (P<0.01). Fifty-nine cases (55.7%) got to extremely ef ective, and 29 cases (27.4%) ef ective. Total ef icient rate was 83.0%. The average quantities of morphine consumption before and after treatment in the patients with grade III pain were 114.9 ± 132.5 mg, 16.8 ± 39.7 mg each person everyday respectively (P<0.01). Conclusion:HIFU can relieve pain suf ered by patients with pancreatic cancer ef ectively. It is a new adjuvant treatment for pancreatic cancer pain.

  20. Treatment of advanced pancreatic cancer with opioid growth factor: phase I.

    Science.gov (United States)

    Smith, Jill P; Conter, Robert L; Bingaman, Sandra I; Harvey, Harold A; Mauger, David T; Ahmad, Mejdi; Demers, Lawrence M; Stanley, Wayne B; McLaughlin, Patricia J; Zagon, Ian S

    2004-03-01

    Opioid growth factor (OGF) is an endogenous pentapeptide that inhibits growth of human pancreatic cancer cells in culture, as well as xenografts in nude mice. To establish the maximum tolerated dose (MTD), and determine safety and toxicity of OGF, a phase I trial was performed in patients with advanced unresectable pancreatic cancer. Patients with unresectable pancreatic adenocarcinoma were treated with escalating doses of OGF for 30 min i.v. to determine the MTD. The s.c. route of administration also was evaluated. Once the MTD was established, a group of patients was treated chronically, and monitored for safety and toxicity. Hypotension was the dose-limiting toxicity, resulting in a MTD of 250 microg/kg i.v. Due to limited solubility of OGF in small volumes, a maximum dose of 50 microg/kg twice daily was determined by the s.c. route of administration. No adverse events were reported for oxygen saturation, cardiac rhythm, laboratory values or neurological status in either the acute or chronic parts of the study with the i.v. or s.c. routes. During the chronic i.v. phase, two subjects had resolution of liver metastases and one showed regression of the pancreatic tumor. Mean survival from the time of diagnosis was 8.7 months (range 2-23 months) in the i.v. group and 9.5 months (range 1-18 months) in the s.c. group. We conclude that OGF can be safely administered to patients with advanced pancreatic cancer. Further studies are needed to determine the efficacy of OGF alone or in combination with present modes of therapy for the treatment of pancreatic cancer.

  1. Radiotherapy Technical Considerations in the Management of Locally Advanced Pancreatic Cancer: American-French Consensus Recommendations

    Energy Technology Data Exchange (ETDEWEB)

    Huguet, Florence, E-mail: florence.huguet@tnn.aphp.fr [Department of Radiation Oncology, Tenon Hospital, APHP, University Paris VI, Paris (France); Goodman, Karyn A. [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Azria, David [Department of Radiation Oncology, CRLC Val d' Aurelle-Paul Lamarque, Montpellier (France); Racadot, Severine [Department of Radiation Oncology, CRLC Leon Berard, Lyon (France); Abrams, Ross A. [Department of Radiation Oncology, Rush University Medical Center, Chicago, Illinois (United States)

    2012-08-01

    Summary: Pancreatic carcinoma is a leading cause of cancer-related mortality. Approximately 30% of pancreatic cancer patients present with locally advanced, unresectable nonmetastatic disease. For these patients, two therapeutic options exist: systemic chemotherapy or chemoradiotherapy. Within this context, the optimal technique for pancreatic irradiation is not clearly defined. A search to identify relevant studies was undertaken using the Medline database. All Phase III randomized trials evaluating the modalities of radiotherapy in locally advanced pancreatic cancer were included, as were some noncontrolled Phase II and retrospective studies. An expert panel convened with members of the Radiation Therapy Oncology Group and GERCOR cooperative groups to review identified studies and prepare the guidelines. Each member of the working group independently evaluated five endpoints: total dose, target volume definition, radiotherapy planning technique, dose constraints to organs at risk, and quality assurance. Based on this analysis of the literature, we recommend either three-dimensional conformal radiation therapy or intensity-modulated radiation therapy to a total dose of 50 to 54 Gy at 1.8 to 2 Gy per fraction. We propose gross tumor volume identification to be followed by an expansion of 1.5 to 2 cm anteriorly, posteriorly, and laterally, and 2 to 3 cm craniocaudally to generate the planning target volume. The craniocaudal margins can be reduced with the use of respiratory gating. Organs at risk are liver, kidneys, spinal cord, stomach, and small bowel. Stereotactic body radiation therapy should not be used for pancreatic cancer outside of clinical trials. Radiotherapy quality assurance is mandatory in clinical trials. These consensus recommendations are proposed for use in the development of future trials testing new chemotherapy combinations with radiotherapy. Not all of these recommendations will be appropriate for trials testing radiotherapy dose or dose

  2. Radiotherapy technical considerations in the management of locally advanced pancreatic cancer: American-French consensus recommendations.

    Science.gov (United States)

    Huguet, Florence; Goodman, Karyn A; Azria, David; Racadot, Severine; Abrams, Ross A

    2012-08-01

    Pancreatic carcinoma is a leading cause of cancer-related mortality. Approximately 30% of pancreatic cancer patients present with locally advanced, unresectable nonmetastatic disease. For these patients, two therapeutic options exist: systemic chemotherapy or chemoradiotherapy. Within this context, the optimal technique for pancreatic irradiation is not clearly defined. A search to identify relevant studies was undertaken using the Medline database. All Phase III randomized trials evaluating the modalities of radiotherapy in locally advanced pancreatic cancer were included, as were some noncontrolled Phase II and retrospective studies. An expert panel convened with members of the Radiation Therapy Oncology Group and GERCOR cooperative groups to review identified studies and prepare the guidelines. Each member of the working group independently evaluated five endpoints: total dose, target volume definition, radiotherapy planning technique, dose constraints to organs at risk, and quality assurance. Based on this analysis of the literature, we recommend either three-dimensional conformal radiation therapy or intensity-modulated radiation therapy to a total dose of 50 to 54 Gy at 1.8 to 2 Gy per fraction. We propose gross tumor volume identification to be followed by an expansion of 1.5 to 2 cm anteriorly, posteriorly, and laterally, and 2 to 3 cm craniocaudally to generate the planning target volume. The craniocaudal margins can be reduced with the use of respiratory gating. Organs at risk are liver, kidneys, spinal cord, stomach, and small bowel. Stereotactic body radiation therapy should not be used for pancreatic cancer outside of clinical trials. Radiotherapy quality assurance is mandatory in clinical trials. These consensus recommendations are proposed for use in the development of future trials testing new chemotherapy combinations with radiotherapy. Not all of these recommendations will be appropriate for trials testing radiotherapy dose or dose intensity

  3. Opioid growth factor improves clinical benefit and survival in patients with advanced pancreatic cancer

    Directory of Open Access Journals (Sweden)

    Jill P Smith

    2010-03-01

    Full Text Available Jill P Smith1, Sandra I Bingaman1, David T Mauger2, Harold H Harvey1, Laurence M Demers3, Ian S Zagon41Departments of Medicine, 2Public Health Sciences, 3Pathology, and 4Neurosciences and Anatomy, Pennsylvania State University, College of Medicine, Hershey Medical Center, Hershey, PA, USABackground: Advanced pancreatic cancer carries the poorest prognosis of all gastrointestinal malignancies. Once the tumor has spread beyond the margins of the pancreas, chemotherapy is the major treatment modality offered to patients; however, chemotherapy does not significantly improve survival.Objective: Opioid growth factor (OGF; [Met5]-enkephalin is a natural peptide that has been shown to inhibit growth of pancreatic cancer in cell culture and in nude mice. The purpose of this study was to evaluate the effects of OGF biotherapy on subjects with advanced pancreatic cancer who failed chemotherapy.Methods: In a prospective phase II open-labeled clinical trial, 24 subjects who failed standard chemotherapy for advanced pancreatic cancer were treated weekly with OGF 250 μg/kg intravenously. Outcomes measured included clinical benefit, tumor response by radiographic imaging, quality of life, and survival.Results: Clinical benefit response was experienced by 53% of OGF-treated patients compared to historical controls of 23.8% and 4.8% for gemcitabine and 5-fluorouracil (5-FU, respectively. Of the subjects surviving more than eight weeks, 62% showed either a decrease or stabilization in tumor size by computed tomography. The median survival time for OGF-treated patients was three times that of untreated patients (65.5 versus 21 days, p < 0.001. No adverse effects on hematologic or chemistry parameters were noted, and quality of life surveys suggested improvement with OGF. Limitations: Measurements other than survival were not allowed in control patients, and clinical benefit comparisons were made to historical controls.Conclusion: OGF biotherapy improves the

  4. Diabetes and pancreatic cancer

    OpenAIRE

    Christine Hsu; Muhammad Wasif Saif

    2012-01-01

    Pancreatic cancer is the fourth leading cause of cancer death in the United States. Risk factors for pancreatic cancer are smoking, family history, chronic pancreatitis, and diabetes. There is controversy with regards to the causal relationship between diabetes and pancreatic cancer because many patients with pancreatic cancer have new onset diabetes. Abstracts presented at the 2011 American Society of Clinical Oncology (ASCO) Annual Meeting highlighted and supported the positive association ...

  5. A patient with unresectable advanced pancreatic cancer achieving long-term survival with Gemcitabine chemotherapy

    Institute of Scientific and Technical Information of China (English)

    Yoshiki Okamoto; Takashi Maeba; Keitarou Kakinoki; Keiichi Okano; Kunihiko Izuishi; Hisao Wakabayashi; Hisashi Usuki; Yasuvuki Suzuki

    2008-01-01

    A 68-year-old female visited a local clinic with epigastralgia. A routine laboratory test revealed jaundice and liver dysfunction. She was referred to this hospital. Abdominal computed tomography (CT) and endoscopic retrograde cholangio-pancreatography (ERCP) revealed that the density of the entire pancreas had decreased, and showed dilatation of the common bile duct (CBD) and the main pancreatic duct (MPD). Pancreatic cancer was diagnosed by cytological examination analyzing the pancreatic juice obtained by ERCP. When jaundice had decreased the tumor was observed via laparotomy. No ascites, liver metastasis, or peritoneal dissemination was observed. The entire pancreas was a hard mass, and a needle biopsy was obtained from the head, body and tail of the pancreas. These biopsies diagnosed a poorly differentiated adenocarcinoma. Hepaticojejunostomy was thus performed, and postoperative progress was good. Chemotherapy with 1000 mg/body per week of gemcitabine was administered beginning 15 d postoperatively. However, the patient suffered relatively severe side effects, and it was necessary to change the dosing schedule of gemcitabine. Abdominal CT revealed a complete response (CR) after 3 treatments. Therefore, weekly chemotherapy was stopped and was changed to monthly administration. To date, for 4 years after chemotherapy, the tumor has not reappeared.Key werds: Gemcitabine; Long-term survival; Unresectable advanced pancreatic cancer

  6. L-Carnitine-supplementation in advanced pancreatic cancer (CARPAN - a randomized multicentre trial

    Directory of Open Access Journals (Sweden)

    Kraft Matthias

    2012-07-01

    Full Text Available Abstract Background Cachexia, a >10% loss of body-weight, is one factor determining the poor prognosis of pancreatic cancer. Deficiency of L-Carnitine has been proposed to cause cancer cachexia. Findings We screened 152 and enrolled 72 patients suffering from advanced pancreatic cancer in a prospective, multi-centre, placebo-controlled, randomized and double-blinded trial to receive oral L-Carnitine (4 g or placebo for 12 weeks. At entry patients reported a mean weight loss of 12 ± 2,5 (SEM kg. During treatment body-mass-index increased by 3,4 ± 1,4% under L-Carnitine and decreased (−1,5 ± 1,4% in controls (p  Conclusion While these data are preliminary and need confirmation they indicate that patients with pancreatic cancer may have a clinically relevant benefit from the inexpensive and well tolerated oral supplementation of L-Carnitine.

  7. Chronic pancreatitis and pancreatic cancer.

    Science.gov (United States)

    Maisonneuve, Patrick; Lowenfels, Albert B

    2002-01-01

    Pancreatic cancer is the fourth leading cause of cancer deaths in the USA in both sexes. Early diagnosis is difficult and the overall mortality rate is high. Individuals at high risk for pancreatic cancer include smokers, and persons with all forms of chronic alcoholic, metabolic, tropical or hereditary pancreatitis. The duration of exposure to inflammation seems to be the major factor involved in the transition from benign to malignant condition. Smoking, which appears to further accelerate the carcinogenic transformation, remains the strongest risk factor amenable to preventive intervention.

  8. Pancreatic cancer: yesterday, today and tomorrow.

    Science.gov (United States)

    Ansari, Daniel; Tingstedt, Bobby; Andersson, Bodil; Holmquist, Fredrik; Sturesson, Christian; Williamsson, Caroline; Sasor, Agata; Borg, David; Bauden, Monika; Andersson, Roland

    2016-08-01

    Pancreatic cancer is one of our most lethal malignancies. Despite substantial improvements in the survival rates for other major cancer forms, pancreatic cancer survival rates have remained relatively unchanged since the 1960s. Pancreatic cancer is usually detected at an advanced stage and most treatment regimens are ineffective, contributing to the poor overall prognosis. Herein, we review the current understanding of pancreatic cancer, focusing on central aspects of disease management from radiology, surgery and pathology to oncology.

  9. Intensity modulated radiation therapy and chemotherapy for locally advanced pancreatic cancer: Results of feasibility study

    Institute of Scientific and Technical Information of China (English)

    Yong-Rui Bai; Guo-Hua Wu; Wei-Jian Guo; Xu-Dong Wu; Yuan Yao; Yin Chen; Ren-Hua Zhou; Dong-Qin Lu

    2003-01-01

    AIM: To explore whether intensity modulated radiation therapy (IMRT) in combination with chemotherapy could increase radiation dose to gross tumor volume without severe acute radiation related toxicity by decreasing the dose to the surrounding normal tissue in patients with locally advanced pancreatic cancer.METHODS: Twenty-one patients with locally advanced pancreatic cancer were evaluated in this clinical trial,Patients would receive the dose of IMRT from 21Gy to 30Gy in 7 to 10 fractions within two weeks after conventional radiotherapy of 30Gy in 15 fractions over 3 weeks. The total escalation tumor dose would be 51, 54,57, 60Gy, respectively. 5-fluororacil (5-FU) or gemcitabine was given concurrently with radiotherapy during the treatment course.RESULTS: Sixteen patients who had completed the radiotherapy plan with doses of 51Gy (3 cases), 54Gy (3 cases), 57Gy (3 cases) and 60Gy (7 cases) were included for evaluation. The median levels of CA19-9 prior to and after radiotherapy were 716 U/ml and 255 U/ml respectively (P<0.001) in 13 patients who demonstrated high levels of CA19-9 before radiotherapy. Fourteen patients who suffered from pain could reduce at least 1/3-1/2 amount of analgesic intake and 5 among these patients got complete relief of pain. Ten patients improved in Kamofsky performance status (KPS). The median follow-up period was 8 months and one-year survival rate was 35 %. No patient suffered more than grade Ⅲ acute toxicities induced by radiotherapy.CONCLUSION: Sixty Gy in 25 fractions over 5 weeks with late course IMRT technique combined with concurrent 5-FU chemotherapy can provide a definitely palliative benefit with tolerable acute radiation related toxicity for patients with advanced pancreatic cancer.

  10. Chemoradiotherapy with twice-weekly administration of low-dose gemcitabine for locally advanced pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    Hisato Igarashi; Tetsuhide Ito; Ken Kawabe; Terumasa Hisano; Yoshiyuki Arita; Toyoma Kaku; Ryoichi Takayanagi

    2008-01-01

    AIM:To evaluate the chemoradiotherapy for locally advanced pancreatic cancer utilizing low dose gemcitabine as a radiation sensitizer administered twice weekly.METHODS:We performed a retrospective analysis of chemoradiotherapy utilizing gemcitabine administered twice weekly at a dose of 40 mg/m2.After that,maintenance systemic chemotherapy with gemcitabine,at a dose of 1000 mg/m2,was administered weekly for 3 wk with 1-wk rest until disease progression or unacceptable toxicity developed.RESULTS:Eighteen patients with locally advanced unresectable pancreatic cancer were enrolled.Three of those patients could not continue with the therapy;one patient had interstitial pneumonia during radiation therapy and two other patients showed liver metastasis or peritoneal metastasis during an early stage of the therapy.The median survival was 15.0 mo and the overall 1-year survival rate was 60%,while the median progression-free survival was 8.0 too.The subgroup which showed the reduction of tumor development,more than 50% showed a tendency for a better prognosis;however,other parameters including age,gender and performance status did not correlate with survival.The median survival of the groups that died of liver metastasis and peritoneal metastasis were 13.0 mo and 27.7 mo,respectively.CONCLUSION:Chemoradiotherapy with low-dose gemcitabine administered twice weekly could be effective to patients with locally advanced pancreatic cancer;however,patients developing liver metastases had a worse prognosis.Another chemoradiotherapy strategy might be needed for those patients,such as administrating one or two cycles of chemotherapy initially,followed by chemoradiotherapy for the cases with no distant metastases.

  11. Outcome after neoadjuvant chemoradiation and correlation with nutritional status in patients with locally advanced pancreatic cancer

    Energy Technology Data Exchange (ETDEWEB)

    Naumann, P.; Habermehl, D.; Welzel, T.; Combs, S.E. [University Clinic Heidelberg (Germany). Dept. of Radiation Oncology; Debus, J. [University Clinic Heidelberg (Germany). Dept. of Radiation Oncology; Deutsches Krebsforschungszentrum, Heidelberg (Germany)

    2013-09-15

    Background: Cancer patients commonly suffer from weight loss since rapid tumor growth can cause catabolic metabolism and depletion of energy stores such as abdominal fat. In locally advanced pancreatic cancer this is even more pronounced due to abdominal pain, fatigue, nausea or malnutrition. In the present article, we quantify this frequently observed weight loss and assess its impact on outcome and survival. Methods: Data on demographics, biometrics, toxicity and survival were collected for the last 100 patients treated with neoadjuvant chemoradiation for locally advanced pancreatic cancer at our department (45.0 Gy and boost up to 54.0 Gy plus concurrent and subsequent gemcitabine), and the subcutaneous fat area at the umbilicus level was measured by computer tomography before and after chemoradiation. Results: After chemoradiation, patients showed a highly statistically significant weight loss and reduction of the subcutaneous fat area. We could determine a very strong correlation of subcutaneous fat area to patient BMI. By categorizing patients according to their BMI based on the WHO classification as slender, normal, overweight and obese, we found improved but not statistically significant survival among obese patients. Accordingly, patients who showed less weight loss tended to survive longer. Conclusions: In this study, patients with pancreatic cancer lost weight during chemoradiation and their subcutaneous fat diminished. Changes in subcutaneous fat area were highly correlated with patients' BMI. Moreover, obese patients and patients who lost less weight had an improved outcome after treatment. Although the extent of weight loss was not significantly correlated with survival, the observed trend warrants greater attention to nutritional status in the future. (orig.)

  12. Inherited pancreatic cancer syndromes.

    Science.gov (United States)

    Solomon, Sheila; Das, Siddhartha; Brand, Randall; Whitcomb, David C

    2012-01-01

    Pancreatic cancer remains one of the most challenging of all cancers. Genetic risk factors are believed to play a major role, but other than genes coding for blood group, genetic risks for sporadic cases remain elusive. However, several germline mutations have been identified that lead to hereditary pancreatic cancer, familial pancreatic cancer, and increased risk for pancreatic cancer as part of a familial cancer syndrome. The most important genes with variants increasing risk for pancreatic cancer include BRCA1, BRCA2, PALB2, ATM, CDKN2A, APC, MLH1, MSH2, MSH6, PMS2, PRSS1, and STK11. Recognition of members of high-risk families is important for understanding pancreatic cancer biology, for recommending risk reduction strategies and, in some cases, initiating cancer surveillance programs. Because the best methods for surveillance have not been established, the recommendation to refer at-risk patients to centers with ongoing research programs in pancreatic cancer surveillance is supported.

  13. Clinical and Immune Effects of Lenalidomide in Combination with Gemcitabine in Patients with Advanced Pancreatic Cancer

    Science.gov (United States)

    Ullenhag, Gustav J.; Mozaffari, Fariba; Broberg, Mats; Mellstedt, Håkan; Liljefors, Maria

    2017-01-01

    Purpose To assess the immunomodulatory and clinical effects of lenalidomide with standard treatment of gemcitabine in patients with advanced pancreatic cancer. Patients and Methods Patients with advanced pancreatic cancer were treated in first line with lenalidomide orally for 21 days of a 28 days cycle and the standard regimen for gemcitabine. In Part I, which we previously have reported, the dose of lenalidomide was defined (n = 12). In Part II, every other consecutive patient was treated with either lenalidomide (Group A, n = 11) or gemcitabine (Group B, n = 10) during cycle 1. From cycle 2 on, all Part II patients received the combination. Results A significant decrease in the proliferative response of peripheral blood mononuclear cells and the frequency of DCs were noted in patients at baseline compared to healthy control donors while the frequencies of CD4+ and CD8+ T cells, NK-cells and MDSCs were significantly higher in patients compared to controls. In Group A, a significant increase in the absolute numbers of activated (HLA-DR+) CD4 and CD8 T cells and CD8 effector memory T cells (pLenalidomide augmented T cell reactivities, which were abrogated by gemcitabine. However, addition of lenalidomide to gemcitabine seemed to have no therapeutic impact compared to gemcitabine alone in this non-randomized study. Trial Registration ClinicalTrials.gov NCT01547260 PMID:28099502

  14. Dynamic Contrast Enhanced MRI in Patients With Advanced Breast or Pancreatic Cancer With Metastases to the Liver or Lung

    Science.gov (United States)

    2014-05-28

    Acinar Cell Adenocarcinoma of the Pancreas; Duct Cell Adenocarcinoma of the Pancreas; Liver Metastases; Lung Metastases; Recurrent Breast Cancer; Recurrent Pancreatic Cancer; Stage IV Breast Cancer; Stage IV Pancreatic Cancer

  15. [The first report from Sapporo Tsukisamu Hospital--chemotherapy and chemoradiotherapy for patients with advanced pancreatic cancer].

    Science.gov (United States)

    Yamamitsu, Susumu; Kimura, Hiromichi; Yamada, Yoshiyuki; Inui, Noriaki; Hiyama, Shigemi; Hirata, Koichi; Kimura, Yasutoshi; Koito, Kazumitsu; Shirasaka, Tetsuhiko

    2007-07-01

    The remedy, especially chemotherapy, for advanced pancreatic cancer is hardly ever successful in terms of efficacy rate and survival period, because it is virtually unable to contribute to the improvement of median survival time (MST). Thus,we devised a new intermittent dosage regimen utilizing the cell cycle difference of normal GI tract, bone marrow cell and pancreatic cancer cell, making use of 5-FU (-->S-1), CDDP and paclitaxel in March 2002. Ten patients with advanced pancreatic cancer (4 in Stage IVa and 6 in Stage IVb) were treated with this new regimen. As a result, an efficacy ratio of 50.0% and a 1-year survival ratio of 60.0% were achieved. However, 2-year survival ratio of 12.0% was low, and there was no 3-year survivor. The MST was 19 months as of December 31, 2006. All of the non-hematological toxicities were under grade 2. Eight patients had hematological toxicities over grade 3 and most of them were anemia and neutropenia. Only 2 cases had thrombocytopenia. Although adverse effects related to this regimen were clinically manageable, it was difficult to improve MST of patients with advanced pancreatic cancer with chemotherapy alone including this regimen. Hence, we devised another regimen with the joint use of radiotherapy along with the same chemotherapy regimen in January 2003. Twenty patients with advanced pancreatic cancer (Stage IV) were treated with this regimen. It is presently under way, and an efficacy ratio of 35.0%, 1-year survival ratio of 86.3% and 2-year survival ratio of 64.0% were obtained by May 2005, showing that this may contribute to the extension of survival time of Stage IV pancreatic cancer patients.

  16. Therapeutic Evaluation on Advanced Pancreatic Cancer Treated by Integrative Chinese and Western Medicine Clinical Analysis of 56 Cases

    Institute of Scientific and Technical Information of China (English)

    刘鲁明; 吴良村; 林胜友; 杨维鸿; 郭勇; 徐颖扉; 舒琦瑾

    2003-01-01

    Objective: In comparison with chemotherapy, to evaluate therapeutic effcts on advanced pancreatic cancer treated by integrative Chinese and western medicine (ICWM) therapies. Methods: Based on the retrospective study of 56 patients with advanced pancreatic cancer,life table was applied to the analysis of patients' survival rate and χ2 test to the comparison of therapeutic response between ICWM and chemotherapy groups. Results: The results showed that 1-year survival rate in the ICWM group was 55.37%±3.24%; 2-year survival rate 34.61%±16.31%; 3-year survival rate 25.96%±24.64%; 5-year survival rate 25.96%±24.64%; and median survival period 16.3 months. However 1-year survival rate in the chemotherapy group was 21.95%±27.54%; 2-year survival rate 7.31%±27.54%; 3-year survival rate 0%; and median survival period 7.5 months. The therapeutic effects between two groups were significantly different (P=0.004). Further analysis suggested that the reduction of cancer mass in the ICWM group was more than that in chemotherapy group (P=0.049) and the improvement of advanced pancreatic cancer related-symptoms better than that of chemotherapy group (P=0.002). Conclusion: The ICWM comprehensive therapy is of important value in the treatment of advanced pancreatic cancer.

  17. Therapeutic Evaluation on Advanced Pancreatic Cancer Treated by Integrative Chinese and Western Medicine—Clinical Analysis of 56 Cases

    Institute of Scientific and Technical Information of China (English)

    LIULu-ming; WULiang-cun; 等

    2003-01-01

    Objective:In comparison with chemotherapy,to evaluate therapeutic effects on advanced pancreatic cancer treated by integrative Chinese and western medicine(ICWM) therapies.Methods:Based on the retrospective study of 56 patients with advanced pancreatic cancer,life table was applied to the anal-ysis of patients' survival rate and X2 test to the comparison of therapeutic response between ICWM and chemotherapy groups.Results:The results showed that 1-year survival rate 25.96%±24.64%; 5-year 37%±3.24%;2-year survival rate 34.61%±16.31%;3-year survival rate 25.96%±24.64%;5-year survival rate 25.96%±24.64%; and median survival period 16.3 months.However 1-year survival rate in the chemotherapy group was 21.95%±27.54%;2-year survival rate 7.31%±27.54%;3-year survival rate 0%; and median survival period 7.5months.The therapeutic effects between two groups were signifi-cantly different(P=0.004).Further analysis suggested that the reduction of cancer mass in the ICWM group was more than that in chemotherapy group(P=0.049) and the improvement of advanced pancreatic cancer related-symptoms better than that of chemotherapy group(P=0.002).Conclusion:The ICWM comprehensive therapy is of important value in the treatment of advanced pancreatic cancer.

  18. Comparing Concurrent Chemoradiotherapy to Chemotherapy Alone for Locally Advanced Unresectable Pancreatic Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Park, Jeong Hoon; Kim, Woo Chul; Kim, Hun Jung; Gwak, Hee Keun [Inha University Hospital, Incheon (Korea, Republic of)

    2009-06-15

    Concurrent chemoradiotherapy (CCRT) is the standard treatment for locally advanced unresectable pancreatic cancer. However, the introduction of gemcitabine and the recognition of a benefit in patients with advanced disease stimulated the design of trials that compare chemotherapy alone to concurrent chemoradiation. Therefore, we evaluated role of CCRT for locally advanced unresectable pancreatic cancer. We carried out a retrospective analysis of treatment results for patients with locally advanced unresectable pancreatic cancer between January 2000 and January 2008. The radiation was delivered to the primary tumor and regional lymph nodes with a 1{approx}2 cm margin at a total dose of 36.0{approx}59.4 Gy (median: 54 Gy). The chemotherapeutic agent delivered with the radiation was 5-FU (500 mg/m{sup 2}). The patients who underwent chemotherapy alone received gemcitabine (1,000 mg/m{sup 2}) alone or gemcitabine with 5-FU. The follow-up period ranged from 2 to 38 months. The survival and prognostic factors were analyzed using Kaplan-Meier method and log-rank test, respectively. Thirty-four patients received concurrent chemoradiotherapy, whereas 21 patients received chemotherapy alone. The median survival time was 12 months for CCRT patients, compared to 11 months for chemotherapy alone patients (p=0.453). The median progression-free survival was 8 months for CCRT patients, compared to 5 months for chemotherapy alone patients (p=0.242). The overall response included 9 partial responses for CCRT and 1 partial response for chemotherapy alone. In total, 26% of patients from the CCRT group experienced grade 3{approx}4 bowel toxicity. In contract, no grade 3{approx}4 bowel toxicity was observed in the chemotherapy alone group. The significant prognostic factors of overall survival were lymph node status, high CA19-9, and tumor location. The response rate and progression-free survival were more favorable in the CCRT group, when compared with the chemotherapy alone group

  19. Survival of patients with advanced pancreatic cancer after iodine125 seeds implantation brachytherapy

    Science.gov (United States)

    Han, Quanli; Deng, Muhong; Lv, Yao; Dai, Guanghai

    2017-01-01

    Abstract Background: Brachytherapy with iodine125-labeled seeds (125I-seeds) implantation is increasingly being used to treat tumors because of its positional precision, minimal invasion, least damage to noncancerous tissue due to slow and continuous release of radioactivity and facilitation with modern medical imaging technologies. This study evaluates the survival and pain relief outcomes of the 125I-seeds implantation brachytherapy in advanced pancreatic cancer patients. Methods: Literature search was carried out in multiple electronic databases (Google Scholar, Embase, Medline/PubMed, and Ovid SP) and studies reporting I125 seeds implantation brachytherapy in pancreatic cancer patients with unresectable tumor were selected by following predetermined eligibility criteria. Random effects meta-analysis was performed to achieve inverse variance weighted effect size of the overall survival rate after the intervention. Sensitivity and subgroups analyses were also carried out. Results: Twenty-three studies (824 patients’ data) were included in the meta-analysis. 125I-seeds implantation brachytherapy alone was associated with 8.98 [95% confidence interval (CI): 6.94, 11.03] months (P < 0.00001) overall survival with 1-year survival of 25.7 ± 9.3% (mean ± standard deviation; SD) and 2-year survival was 17.9 ± 8.6% (mean ± SD). In stage IV pancreatic cancer patients, overall survival was 7.13 [95% CI: 4.75, 9.51] months (P < 0.00001). In patients treated with 125I-seeds implantation along with 1 or more therapies, overall survival was 11.75 [95% CI: 9.84, 13.65] months (P < 0.00001) with 1-year survival of 47.4 ± 22.75% (mean ± SD) and 2-year survival was 16.97 ± 3.1% (mean ± SD). 125I-seeds brachytherapy was associated with relief of pain in 79.7 ± 9.9% (mean ± SD) of the patients. Conclusions: Survival of pancreatic cancer patients after 125I-seeds implantation brachytherapy is found to be 9 months

  20. Prognostic factors and sites of metastasis in unresectable locally advanced pancreatic cancer.

    Science.gov (United States)

    Peixoto, Renata D'Alpino; Speers, Caroline; McGahan, Colleen E; Renouf, Daniel J; Schaeffer, David F; Kennecke, Hagen F

    2015-08-01

    Due to differences in natural history and therapy, clinical trials of patients with advanced pancreatic cancer have recently been subdivided into unresectable locally advanced pancreatic cancer (LAPC) and metastatic disease. We aimed to evaluate prognostic factors in LAPC patients who were treated with first-line chemotherapy and describe patterns of disease progression. Patients with LAPC who initiated first-line palliative chemotherapy, 2001-2011 at the BC Cancer Agency were included. A retrospective chart review was conducted to identify clinicopathologic variables, treatment, and subsequent sites of metastasis. Kaplan-Meier and Cox-regression survival analyses were performed. A total of 244 patients were included in this study. For the majority of patients (94.3%), first-line therapy was single-agent gemcitabine. About 144 (59%) patients developed distant metastatic disease and the most frequent metastatic sites included peritoneum/omentum (42.3%), liver (41%), lungs (13.9%), and distant lymph nodes (9%). Median overall survival (OS) for the entire cohort was 11.7 months (95% CI, 10.6-12.8). Development of distant metastases was associated with significantly inferior survival (HR 3.56, 95% CI 2.57-4.93), as was ECOG 2/3 versus 0/1 (HR 1.69, 95% CI 1.28-2.23), CA 19.9 > 1000 versus ≤ 1000 (HR 1.59, 95% CI 1.19-2.14) and female gender, (HR 1.57, 95% CI 1.19-2.08). In this population-based study, 41% of LAPC patients treated with first-line chemotherapy died without evidence of distant metastases. Prognostic factors for LAPC were baseline performance status, elevated CA 19.9, gender, and development of distant metastasis. Results highlight the heterogeneity of LAPC and the importance of locoregional tumor control.

  1. Hypermutation In Pancreatic Cancer.

    Science.gov (United States)

    Humphris, Jeremy L; Patch, Ann-Marie; Nones, Katia; Bailey, Peter J; Johns, Amber L; McKay, Skye; Chang, David K; Miller, David K; Pajic, Marina; Kassahn, Karin S; Quinn, Michael C J; Bruxner, Timothy J C; Christ, Angelika N; Harliwong, Ivon; Idrisoglu, Senel; Manning, Suzanne; Nourse, Craig; Nourbakhsh, Ehsan; Stone, Andrew; Wilson, Peter J; Anderson, Matthew; Fink, J Lynn; Holmes, Oliver; Kazakoff, Stephen; Leonard, Conrad; Newell, Felicity; Waddell, Nick; Wood, Scott; Mead, Ronald S; Xu, Qinying; Wu, Jianmin; Pinese, Mark; Cowley, Mark J; Jones, Marc D; Nagrial, Adnan M; Chin, Venessa T; Chantrill, Lorraine A; Mawson, Amanda; Chou, Angela; Scarlett, Christopher J; Pinho, Andreia V; Rooman, Ilse; Giry-Laterriere, Marc; Samra, Jaswinder S; Kench, James G; Merrett, Neil D; Toon, Christopher W; Epari, Krishna; Nguyen, Nam Q; Barbour, Andrew; Zeps, Nikolajs; Jamieson, Nigel B; McKay, Colin J; Carter, C Ross; Dickson, Euan J; Graham, Janet S; Duthie, Fraser; Oien, Karin; Hair, Jane; Morton, Jennifer P; Sansom, Owen J; Grützmann, Robert; Hruban, Ralph H; Maitra, Anirban; Iacobuzio-Donahue, Christine A; Schulick, Richard D; Wolfgang, Christopher L; Morgan, Richard A; Lawlor, Rita T; Rusev, Borislav; Corbo, Vincenzo; Salvia, Roberto; Cataldo, Ivana; Tortora, Giampaolo; Tempero, Margaret A; Hofmann, Oliver; Eshleman, James R; Pilarsky, Christian; Scarpa, Aldo; Musgrove, Elizabeth A; Gill, Anthony J; Pearson, John V; Grimmond, Sean M; Waddell, Nicola; Biankin, Andrew V

    2017-01-01

    Pancreatic cancer is molecularly diverse, with few effective therapies. Increased mutation burden and defective DNA repair are associated with response to immune checkpoint inhibitors in several other cancer types. We interrogated 385 pancreatic cancer genomes to define hypermutation and its causes. Mutational signatures inferring defects in DNA repair were enriched in those with the highest mutation burdens. Mismatch repair deficiency was identified in 1% of tumors harboring different mechanisms of somatic inactivation of MLH1 and MSH2. Defining mutation load in individual pancreatic cancers and the optimal assay for patient selection may inform clinical trial design for immunotherapy in pancreatic cancer.

  2. Mouse models of pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    Marta Herreros-Villanueva; Elizabeth Hijona; Angel Cosme; Luis Bujanda

    2012-01-01

    Pancreatic cancer is one of the most lethal of human malignancies ranking 4th among cancer-related death in the western world and in the United States,and potent therapeutic options are lacking.Although during the last few years there have been important advances in the understanding of the molecular events responsible for the development of pancreatic cancer,currently specific mechanisms of treatment resistance remain poorly understood and new effective systemic drugs need to be developed and probed.In vivo models to study pancreatic cancer and approach this issue remain limited and present different molecular features that must be considered in the studies depending on the purpose to fit special research themes.In the last few years,several genetically engineered mouse models of pancreatic exocrine neoplasia have been developed.These models mimic the disease as they reproduce genetic alterations implicated in the progression of pancreatic cancer.Genetic alterations such as activating mutations in KRas,or TGFb and/or inactivation of tumoral suppressors such as p53,INK4A/ARF BRCA2 and Smad4 are the most common drivers to pancreatic carcinogenesis and have been used to create transgenic mice.These mouse models have a spectrum of pathologic changes,from pancreatic intraepithelial neoplasia to lesions that progress histologically culminating in fully invasive and metastatic disease and represent the most useful preclinical model system.These models can characterize the cellular and molecular pathology of pancreatic neoplasia and cancer and constitute the best tool to investigate new therapeutic approaches,chemopreventive and/or anticancer treatments.Here,we review and update the current mouse models that reproduce different stages of human pancreatic ductal adenocarcinoma and will have clinical relevance in future pancreatic cancer developments.

  3. Importance of performance status for treatment outcome in advanced pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    Stefan Boeck; Axel Hinke; Ralf Wilkowski; Volker Heinemann

    2007-01-01

    Despite progress in the treatment of advanced and metastatic pancreatic cancer (PC), the outcome of this disease remains dismal for the majority of patients.Given the moderate efficacy of treatment, prognostic factors may help to guide treatment decisions. Several trials identified baseline performance status as an important prognostic factor for survival. Unfit patients with a Karnofsky performance status (KPS) below 70% only have a marginal benefit from chemotherapy with gemcitabine (Gem) and may often benefit more from optimal supportive care. Once, however, the decision is taken to apply chemotherapy, KPS may be used to select either mono- or combination chemotherapy. Patients with a good performance status (KPS = 90%-100%) may have a significant and clinically relevant survival benefit from combination chemotherapy. By contrast, patients with a poor performance status (KPS ≤ 80%) have no advantage from intensified therapy and should rather receive single-agent treatment.

  4. Pancreatic Cancer Risk Factors

    Science.gov (United States)

    ... risks of other cancers (or other health problems). Examples of genetic syndromes that can cause exocrine pancreatic cancer include: Hereditary breast and ovarian cancer syndrome , caused by mutations in the BRCA1 or BRCA2 genes Familial atypical ...

  5. Hereditary pancreatitis and secondary screening for early pancreatic cancer.

    Science.gov (United States)

    Vitone, L J; Greenhalf, W; Howes, N R; Neoptolemos, J P

    2005-01-01

    Hereditary pancreatitis is an autosomal dominant disease with incomplete penetrance (80%), accounting for approximately 1% of all cases of pancreatitis. It is characterized by the onset of recurrent attacks of acute pancreatitis in childhood and frequent progression to chronic pancreatitis. Whitcomb et al. identified the cationic trypsinogen gene (PRSS1) on chromosome 7q35 as the site of the mutation that causes hereditary pancreatitis. The European registry of hereditary pancreatitis and familial pancreatic cancer (EUROPAC) aims to identify and make provisions for those affected by hereditary pancreatitis and familial pancreatic cancer. The most common mutations in hereditary pancreatitis are R122H, N29I and A16V but many families have been described with clinically defined hereditary pancreatitis where there is no PRSS1 mutation. It is known that the cumulative lifetime risk (to age 70 years) of pancreatic cancer is 40% in individuals with hereditary pancreatitis. This subset of individuals form an ideal group for the development of a screening programme aimed at detecting pancreatic cancer at an early stage in an attempt to improve the presently poor long-term survival. Current screening strategies involve multimodality imaging (computed tomography, endoluminal ultrasound) and endoscopic retrograde cholangiopancreatography for pancreatic juice collection followed by molecular analysis of the DNA extracted from the juice. The potential benefit of screening (curative resection) must be balanced against the associated morbidity and mortality of surgery. Philosophically, the individual's best interest must be sought in light of the latest advances in medicine and science following discussions with a multidisciplinary team in specialist pancreatic centres.

  6. Familial pancreatic cancer.

    Science.gov (United States)

    Klein, A P; Hruban, R H; Brune, K A; Petersen, G M; Goggins, M

    2001-01-01

    Pancreatic cancer is the fourth leading cause of cancer death in both men and women in the United States and will be responsible for an estimated 28,900 deaths in 2001. Relatively little is known of its etiology, and the only well-established risk factor is cigarette smoking. Studies over the past 3 decades have shown that 4%-16% of patients with pancreatic cancer have a family history of the disease. A small fraction of this aggregation can be accounted for in inherited cancer syndromes, including familial atypical multiple-mole melanoma, Peutz-Jeghers syndrome, hereditary breast-ovarian cancer, hereditary pancreatitis, and hereditary nonpolyposis colorectal cancer. These syndromes arise as a result of germline mutations in the BRCA2, pl6 (familial atypical multiple-mole melanoma), mismatch repair (hereditary nonpolyposis colorectal cancer), and STK11 (Peutz-Jeghers syndrome) genes. In addition, hereditary plays a role in predisposing certain patients with apparently sporadic pancreatic cancer. Many patients with pancreatic cancers caused by a germline mutation in a cancer-causing gene do not have a pedigree that is suggestive of a familial cancer syndrome. A recent prospective analysis of the pedigrees in the National Familial Pancreatic Tumor Registry found that individuals with a family history of pancreatic cancer in multiple first-degree relatives have a high risk of pancreatic cancer themselves. The identification of such high-risk individuals will help clinicians target screening programs and develop preventive interventions with the hope of reducing the mortality of pancreatic cancer in these families.

  7. Molecular biology of pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    Miroslav Zavoral; Petra Minarikova; Filip Zavada; Cyril Salek; Marek Minarik

    2011-01-01

    In spite of continuous research efforts directed at early detection and treatment of pancreatic cancer, the outlook for patients affected by the disease remains dismal. With most cases still being diagnosed at advanced stages, no improvement in survival prognosis is achieved with current diagnostic imaging approaches. In the absence of a dominant precancerous condition, several risk factors have been identified including family history, chronic pancreatitis, smoking, diabetes mellitus, as well as certain genetic disorders such as hereditary pancreatitis, cystic fibrosis, familial atypical multiple Most pancreatic carcinomas, however, remain sporadic. Current progress in experimental molecular techniques has enabled detailed understanding of the molecular processes of pancreatic cancer development. According to the latest information, malignant pancreatic transformation involves multiple oncogenes and tumor-suppressor genes that are involved in a variety of signaling pathways. The most characteristic aberrations (somatic point mutations and allelic losses) affect oncogenes and tumor-suppressor genes within RAS, AKT and Wnt signaling, and have a key role in transcription and proliferation, as well as systems that regulate the cell cycle (SMAD/DPC, CDKN2A/p16) and apoptosis (TP53). Understanding of the underlying molecular mechanisms should promote development of new methodology for early diagnosis and facilitate improvement in current approaches for pancreatic cancer treatment.

  8. Pharmacogenomics Update in Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Aditi Puri

    2014-03-01

    Full Text Available Pancreatic cancer is the fourth leading cause of cancer-related deaths in United States. Despite advances in understandingcancer biology and therapeutics, this malignancy carries a grave prognosis with a poor overall survival rate. This is especiallytrue for patients with locally advanced and metastatic disease that are not amenable to surgical resection. Given advances inhuman genome sequencing and pharmacogenomics, we now better understand the complex genetic makeup of these tumorsand numerous gene mutations have been identified that could be potential targets for drug development. In this review, wediscuss two abstract (Abstracts #208 and #192 presented at the 2014 ASCO Gastrointestinal Cancers Symposium aboutpancreatic cancer genome sequencing and their implications for the future of this disease. We discuss what is known aboutthe genome of pancreatic tumors, including common mutations like KRAS, TP53 and SMAD4, as well as discovery ofadditional mutations. In particular, KRAS2 mutations in a subset of patients with pancreatic cancer are discussed. Whilelimited in size and clinical correlativity, these abstracts provide at least seven novel/targetable mutations and elucidatebiologic differences in tumors with wild type and mutant KRAS. These are important steps in understanding tumor biologyand genetic basis of pancreatic cancer to help develop targeted drug therapies in the fast approaching era of personalizedmedicine.

  9. Paclitaxel-Based Chemotherapy for Advanced Pancreatic Cancer after Gemcitabine-Based Therapy Failure: A Case Series of 5 Patients

    Directory of Open Access Journals (Sweden)

    Hisato Igarashi

    2011-11-01

    Full Text Available Background/Objectives: Gemcitabine (GEM is a gold-standard chemotherapy agent for advanced pancreatic cancer. Because of the malignant character of the disease, nearly all patients show disease progression despite treatment with GEM-based chemotherapy; therefore, second-line chemotherapy may be beneficial for these patients. We report a retrospective analysis of 5 patients with advanced pancreatic cancer, treated with a paclitaxel-containing regimen as second-, third- or fourth-line chemotherapy after various therapies, such as a GEM-based regimen, S-1 regimen, and chemoradiation. We retrospectively analyzed the efficacy and adverse events, and evaluated the paclitaxel-containing regimens. A review of the literature is also discussed. Results: The median overall survival from the start of salvage therapy was 10.7 months. The disease control rate of the paclitaxel-containing regimen according to RECIST criteria was 60%, including complete response in 0 patients, partial response in 3, and stable disease in 2. Two patients had malignant ascites at the start of this salvage therapy, and in both of them the ascites and clinical complaints improved. Grade 3 and 4 hematological adverse events were observed in 2 patients and 1 patient, respectively. Conclusion: Salvage paclitaxel-based therapy could be beneficial to advanced pancreatic cancer patients who maintain good performance status after several chemotherapy failures.

  10. Genetic abnormalities in pancreatic cancer

    Directory of Open Access Journals (Sweden)

    Zamboni Giuseppe

    2003-01-01

    Full Text Available Abstract The incidence and mortality of pancreatic adenocarcinoma are nearly coincident having a five-year survival of less than 5%. Enormous advances have been made in our knowledge of the molecular alterations commonly present in ductal cancer and other pancreatic malignancies. One significant outcome of these studies is the recognition that common ductal cancers have a distinct molecular fingerprint compared to other nonductal or endocrine tumors. Ductal carcinomas typically show alteration of K-ras, p53, p16INK4, DPC4 and FHIT, while other pancreatic tumor types show different aberrations. Among those tumors arising from the exocrine pancreas, only ampullary cancers have a molecular fingerprint that may involve some of the same genes most frequently altered in common ductal cancers. Significant molecular heterogeneity also exists among pancreatic endocrine tumors. Nonfunctioning pancreatic endocrine tumors have frequent mutations in MEN-1 and may be further subdivided into two clinically relevant subgroups based on the amount of chromosomal alterations. The present review will provide a brief overview of the genetic alterations that have been identified in the various subgroups of pancreatic tumors. These results have important implications for the development of genetic screening tests, early diagnosis, and prognostic genetic markers.

  11. Updates on Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Ojas Vyas

    2014-05-01

    Full Text Available Pancreatic adenocarcinoma remains a therapeutic challenge. The American Cancer Society estimates that in 2014 about 46,420 people will be diagnosed with pancreatic cancer and about 39,590 people will die of pancreatic cancer in the United States [1]. The incidence of pancreatic carcinoma has markedly increased over the past several decades and it now ranks as the fourth leading cause of cancer-related death in the United States. Despite the high mortality rate associated with pancreatic cancer, its etiology is poorly understood. Although progress in the development of new cytotoxic and biological drugs for the treatment of pancreatic cancer continues, the outcome remains grim. Many organizations and associations have taken an effort to improve knowledge, understanding and outcome of patients with pancreatic cancer. Pancreas Club, since its founding in 1966, is aimed to promote the interchange of ideas between physicians and scientists focused on pancreas throughout the world in an informal “club” atmosphere. We attended the 48th Annual Meeting of Pancreas Club in Chicago and reviewed many interesting posters and oral presentations. Here we discuss a few selected abstracts.

  12. Long-term results of intraoperative electron beam radiation therapy for nonmetastatic locally advanced pancreatic cancer

    Science.gov (United States)

    Chen, Yingtai; Che, Xu; Zhang, Jianwei; Huang, Huang; Zhao, Dongbing; Tian, Yantao; Li, Yexiong; Feng, Qinfu; Zhang, Zhihui; Jiang, Qinglong; Zhang, Shuisheng; Tang, Xiaolong; Huang, Xianghui; Chu, Yunmian; Zhang, Jianghu; Sun, Yuemin; Zhang, Yawei; Wang, Chengfeng

    2016-01-01

    Abstract To assess prognostic benefits of intraoperative electron beam radiation therapy (IOERT) in patients with nonmetastatic locally advanced pancreatic cancer (LAPC) and evaluate optimal adjuvant treatment after IOERT. A retrospective cohort study using prospectively collected data was conducted at the Cancer Hospital of the Chinese Academy of Medical Sciences, China National Cancer Center. Two hundred forty-seven consecutive patients with nonmetastatic LAPC who underwent IOERT between January 2008 and May 2015 were identified and included in the study. Overall survival (OS) was calculated from the day of IOERT. Prognostic factors were examined using Cox proportional hazards models. The 1-, 2-, and 3-year actuarial survival rates were 40%, 14%, and 7.2%, respectively, with a median OS of 9.0 months. On multivariate analysis, an IOERT applicator diameter < 6 cm (hazards ratio [HR], 0.67; 95% confidence interval [CI], 0.47–0.97), no intraoperative interstitial sustained-release 5-fluorouracil chemotherapy (HR, 0.46; 95% CI, 0.32–0.66), and receipt of postoperative chemoradiotherapy followed by chemotherapy (HR, 0.11; 95% CI, 0.04–0.25) were significantly associated with improved OS. Pain relief after IOERT was achieved in 111 of the 117 patients, with complete remission in 74 and partial remission in 37. Postoperative complications rate and mortality were 14.0% and 0.4%, respectively. Nonmetastatic LAPC patients with smaller size tumors could achieve positive long-term survival outcomes with a treatment strategy incorporating IOERT and postoperative adjuvant treatment. Chemoradiotherapy followed by chemotherapy might be a recommended adjuvant treatment strategy for well-selected cases. Intraoperative interstitial sustained-release 5-fluorouracil chemotherapy should not be recommended for patients with nonmetastatic LAPC. PMID:27661028

  13. Danish Pancreatic Cancer Database

    DEFF Research Database (Denmark)

    Fristrup, Claus; Detlefsen, Sönke; Palnæs Hansen, Carsten

    2016-01-01

    AIM OF DATABASE: The Danish Pancreatic Cancer Database aims to prospectively register the epidemiology, diagnostic workup, diagnosis, treatment, and outcome of patients with pancreatic cancer in Denmark at an institutional and national level. STUDY POPULATION: Since May 1, 2011, all patients......, and survival. The results are published annually. CONCLUSION: The Danish Pancreatic Cancer Database has registered data on 2,217 patients with microscopically verified ductal adenocarcinoma of the pancreas. The data have been obtained nationwide over a period of 4 years and 2 months. The completeness...

  14. Pancreatic groove cancer

    Science.gov (United States)

    Ku, Yuan-Hao; Chen, Shih-Chin; Shyr, Bor-Uei; Lee, Rheun-Chuan; Shyr, Yi-Ming; Wang, Shin-E.

    2017-01-01

    Abstract Pancreatic groove cancer is very rare and can be indistinguishable from groove pancreatitis. This study is to clarify the characteristics, clinical features, managements, and survival outcomes of this rare tumor. Brief descriptions were made for each case of pancreatic groove cancer encountered at our institute. Individualized data of pancreatic groove cancer cases described in the literature were extracted and added to our database to expand the study sample size for a more complete analysis. A total of 33 patients with pancreatic groove cancer were included for analysis, including 4 cases from our institute. The median tumor size was 2.7 cm. The most common symptom was nausea or vomiting (89%), followed by jaundice (67%). Duodenal stenosis was noted by endoscopy in 96% of patients. The histopathological examination revealed well differentiated tumor in 43%. Perineural invasion was noted in 90%, and lymphovascular invasion and lymph node involvement in 83%. Overall 1-year survival rate was 93.3%, and 3- or 5-year survival rate was 62.2%, with a median survival of 11.0 months. Survival outcome for the well-differentiated tumors was better than those of the moderate/poorly differentiated ones. Early involvement of duodenum causing vomiting is often the initial presentation, but obstructive jaundice does not always happen until the disease progresses. Tumor differentiation is a prognostic factor for survival outcome. The possibility of pancreatic groove cancer should be carefully excluded before making the diagnosis of groove pancreatitis for any questionable case. PMID:28079795

  15. Hedgehog signaling and therapeutics in pancreatic cancer.

    LENUS (Irish Health Repository)

    Kelleher, Fergal C

    2012-02-01

    OBJECTIVE: To conduct a systematic review of the role that the hedgehog signaling pathway has in pancreatic cancer tumorigenesis. METHOD: PubMed search (2000-2010) and literature based references. RESULTS: Firstly, in 2009 a genetic analysis of pancreatic cancers found that a core set of 12 cellular signaling pathways including hedgehog were genetically altered in 67-100% of cases. Secondly, in vitro and in vivo studies of treatment with cyclopamine (a naturally occurring antagonist of the hedgehog signaling pathway component; Smoothened) has shown that inhibition of hedgehog can abrogate pancreatic cancer metastasis. Thirdly, experimental evidence has demonstrated that sonic hedgehog (Shh) is correlated with desmoplasia in pancreatic cancer. This is important because targeting the Shh pathway potentially may facilitate chemotherapeutic drug delivery as pancreatic cancers tend to have a dense fibrotic stroma that extrinsically compresses the tumor vasculature leading to a hypoperfusing intratumoral circulation. It is probable that patients with locally advanced pancreatic cancer will derive the greatest benefit from treatment with Smoothened antagonists. Fourthly, it has been found that ligand dependent activation by hedgehog occurs in the tumor stromal microenvironment in pancreatic cancer, a paracrine effect on tumorigenesis. Finally, in pancreatic cancer, cells with the CD44+CD24+ESA+ immunophenotype select a population enriched for cancer initiating stem cells. Shh is increased 46-fold in CD44+CD24+ESA+ cells compared with normal pancreatic epithelial cells. Medications that destruct pancreatic cancer initiating stem cells are a potentially novel strategy in cancer treatment. CONCLUSIONS: Aberrant hedgehog signaling occurs in pancreatic cancer tumorigenesis and therapeutics that target the transmembrane receptor Smoothened abrogate hedgehog signaling and may improve the outcomes of patients with pancreatic cancer.

  16. Pancreatic cancer risk in hereditary pancreatitis

    Directory of Open Access Journals (Sweden)

    Frank Ulrich Weiss

    2014-02-01

    Full Text Available Inflammation is part of the body’s immune response in order to remove harmful stimuli – like pathogens, irritants or damaged cells - and start the healing process. Recurrent or chronic inflammation on the other side seems a predisposing factor for carcinogenesis and has been found associated with cancer development. In chronic pancreatitis mutations of the cationic trypsinogen (PRSS1 gene have been identified as risk factors of the disease. Hereditary pancreatitis is a rare cause of chronic pancreatic inflammation with an early onset, mostly during childhood. Hereditary pancreatitis often starts with recurrent episodes of acute pancreatitis and the clinical phenotype is not very much different from other etiologies of the disease. The long-lasting inflammation however generates a tumor promoting environment and represents a major risk factor for tumor development This review will reflect our knowledge concerning the specific risk of hereditary pancreatitis patients to develop pancreatic cancer.

  17. Efficacy and safety of gemcitabine plus erlotinib for locally advanced or metastatic pancreatic cancer: a systematic review and meta-analysis

    Directory of Open Access Journals (Sweden)

    Wang Y

    2016-06-01

    Full Text Available Yuan Wang,1 Guo-fang Hu,1 Qian-qian Zhang,1 Ning Tang,1 Jun Guo,2 Li-yan Liu,2 Xiao Han,2 Xia Wang,2 Zhe-hai Wang2 1School of Medicine and Life Sciences, Shandong Academy of Medical Sciences, University of Jinan, 2Shandong Cancer Hospital, Shandong University, Jinan, Shandong, People’s Republic of China Background: Pancreatic cancer is considered as a chemoresistant neoplasm with extremely dismal prognosis. Gemcitabine is recommended as the standard agent for locally advanced or metastatic pancreatic cancer. A series of trials have been conducted to improve the outcome of advanced pancreatic cancer with other anticancer drugs in combination with gemcitabine. Unfortunately, the designers of the clinical trials failed to improve the poor prognosis of patients with advanced pancreatic cancer. Erlotinib was the first additional drug that improved the overall survival of patients with advanced pancreatic cancer with gemcitabine. We performed this systematic review and meta-analysis to explore the efficacy and safety of the combination of gemcitabine with erlotinib (GemErlo for patients with advanced pancreatic cancer using the currently available evidence. Methods: PubMed/MEDLINE, EMBASE, the Cochrane Library, and relevant abstracts of major conferences were comprehensively searched. Data results on objective response rate, disease control rate, and 1-year survival were pooled by using MetaAnalyst with a random-effects model. Results on progression-free survival and overall survival were only summarized descriptively. Results: A total of 24 studies with 1,742 patients with locally advanced or metastatic pancreatic cancer treated with GemErlo were included. Combined objective response rate was 14.4% (95% CI: 11.6%–17.7%, disease control rate was 55.0% (95% CI: 51.5%–58.5%, and 1-year survival rate was 28.5% (95% CI: 24.0%–33.4%. Progression-free survival ranged from 2.63 to 9.6 months, and overall survival varied from 6 to 10 months. As

  18. Inhibition of the mammalian target of rapamycin (mTOR in advanced pancreatic cancer: results of two phase II studies

    Directory of Open Access Journals (Sweden)

    Zhang Yujian

    2010-07-01

    Full Text Available Abstract Background The phosphoinositide 3-kinase (PI3K/Akt pathway is constitutively activated in pancreatic cancer and the mammalian target of rapamycin (mTOR kinase is an important mediator for its signaling. Our recent in vitro studies suggest that prolonged exposure of pancreatic cancer cells to mTOR inhibitors can promote insulin receptor substrate-PI3K interactions and paradoxically increase Akt phosphorylation and cyclin D1 expression in pancreatic cancer cells (negative feedback loop. The addition of erlotinib to rapamycin can down-regulate rapamycin-stimulated Akt and results in synergistic antitumor activity with erlotinib in preclinical tumor models. Methods Two studies prospectively enrolled adult patients with advanced pancreatic cancer, Eastern Cooperative Oncology Group performance status 0-1, adequate hematologic, hepatic and renal parameters and measurable disease. In Study A, temsirolimus was administered intravenously at 25 mg weekly. In Study B, everolimus was administered orally at 30 mg weekly and erlotinib was administered at 150 mg daily. The primary endpoint in both studies was overall survival at 6 months. Secondary endpoints included time to progression, progression-free survival, overall survival, response rate, safety and toxicity. Pretreatment tumor biopsies were analyzed by immunofluorescence and laser scanning cytometry for the expression of pmTOR/mTOR, pAkt/Akt, pErk/Erk, pS6, p4EBP-1 and PTEN. Results Five patients enrolled in Study A; Two patients died within a month (rapid disease progression and hemorrhagic stroke, respectively. One patient developed dehydration and another developed asthenia. Sixteen patients enrolled in Study B.: 12 males, all ECOG PS = 1. Median cycles = 1 (range 1-2. Grade 4 toxicity: hyponatremia (n = 1, Grade 3: diarrhea (n = 1, cholangitis (n = 3, hyperglycemia (n = 1, fatigue (n = 1. Grade 2: pneumonia (n = 2, dehydration (n = 2, nausea (n = 2, neutropenia (n = 1, mucositis (n = 2

  19. Reverse-Contrast Imaging and Targeted Radiation Therapy of Advanced Pancreatic Cancer Models

    Energy Technology Data Exchange (ETDEWEB)

    Thorek, Daniel L.J., E-mail: dthorek1@jhmi.edu [Division of Nuclear Medicine, The Russell H. Morgan Department of Radiology and Radiological Sciences, The Johns Hopkins School of Medicine, Baltimore, MD (United States); Kramer, Robin M. [Tri-Institutional Training Program in Laboratory Animal Medicine and Science, Memorial Sloan-Kettering Cancer Center (MSKCC), Weill Cornell Medical College, The Rockefeller University, New York, NY (United States); Chen, Qing; Jeong, Jeho; Lupu, Mihaela E. [Department of Medical Physics, MSKCC, New York, NY (United States); Lee, Alycia M.; Moynahan, Mary E.; Lowery, Maeve [Department of Medicine, MSKCC, New York, NY (United States); Ulmert, David [Molecular Pharmacology and Chemistry Program, MSKCC, New York, NY (United States); Department of Surgery (Urology), Skåne University Hospital, Malmö (Sweden); Zanzonico, Pat; Deasy, Joseph O.; Humm, John L. [Department of Medical Physics, MSKCC, New York, NY (United States); Russell, James, E-mail: russellj@mskcc.org [Department of Medical Physics, MSKCC, New York, NY (United States)

    2015-10-01

    Purpose: To evaluate the feasibility of delivering experimental radiation therapy to tumors in the mouse pancreas. Imaging and treatment were performed using combined CT (computed tomography)/orthovoltage treatment with a rotating gantry. Methods and Materials: After intraperitoneal administration of radiopaque iodinated contrast, abdominal organ delineation was performed by x-ray CT. With this technique we delineated the pancreas and both orthotopic xenografts and genetically engineered disease. Computed tomographic imaging was validated by comparison with magnetic resonance imaging. Therapeutic radiation was delivered via a 1-cm diameter field. Selective x-ray radiation therapy of the noninvasively defined orthotopic mass was confirmed using γH2AX staining. Mice could tolerate a dose of 15 Gy when the field was centered on the pancreas tail, and treatment was delivered as a continuous 360° arc. This strategy was then used for radiation therapy planning for selective delivery of therapeutic x-ray radiation therapy to orthotopic tumors. Results: Tumor growth delay after 15 Gy was monitored, using CT and ultrasound to determine the tumor volume at various times after treatment. Our strategy enables the use of clinical radiation oncology approaches to treat experimental tumors in the pancreas of small animals for the first time. We demonstrate that delivery of 15 Gy from a rotating gantry minimizes background healthy tissue damage and significantly retards tumor growth. Conclusions: This advance permits evaluation of radiation planning and dosing parameters. Accurate noninvasive longitudinal imaging and monitoring of tumor progression and therapeutic response in preclinical models is now possible and can be expected to more effectively evaluate pancreatic cancer disease and therapeutic response.

  20. High-dose Helical Tomotherapy With Concurrent Full-dose Chemotherapy for Locally Advanced Pancreatic Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Jee Suk [Department of Radiation Oncology, Yonsei University College of Medicine, Seoul (Korea, Republic of); Wang, Michael L.C. [Department of Radiation Oncology, National Cancer Centre (Singapore); Koom, Woong Sub; Yoon, Hong In; Chung, Yoonsun [Department of Radiation Oncology, Yonsei University College of Medicine, Seoul (Korea, Republic of); Song, Si Young [Department of Internal Medicine, Yonsei University College of Medicine, Seoul (Korea, Republic of); Seong, Jinsil, E-mail: jsseong@yuhs.ac [Department of Radiation Oncology, Yonsei University College of Medicine, Seoul (Korea, Republic of)

    2012-08-01

    Purpose: To improve poor therapeutic outcome of current practice of chemoradiotherapy (CRT), high-dose helical tomotherapy (HT) with concurrent full-dose chemotherapy has been performed on patients with locally advanced pancreatic cancer (LAPC), and the results were analyzed. Methods and Materials: We retrospectively reviewed 39 patients with LAPC treated with radiotherapy using HT (median, 58.4 Gy; range, 50.8-59.9 Gy) and concomitant chemotherapy between 2006 and 2009. Radiotherapy was directed to the primary tumor with a 0.5-cm margin without prophylactic nodal coverage. Twenty-nine patients (79%) received full-dose (1000 mg/m{sup 2}) gemcitabine-based chemotherapy during HT. After completion of CRT, maintenance chemotherapy was administered to 37 patients (95%). Results: The median follow-up was 15.5 months (range, 3.4-43.9) for the entire cohort, and 22.5 months (range, 12.0-43.9) for the surviving patients. The 1- and 2-year local progression-free survival rates were 82.1% and 77.3%, respectively. Eight patients (21%) were converted to resectable status, including 1 with a pathological complete response. The median overall survival and progression-free survival were 21.2 and 14.0 months, respectively. Acute toxicities were acceptable with no gastrointestinal (GI) toxicity higher than Grade 3. Severe late GI toxicity ({>=}Grade 3) occurred in 10 patients (26%); 1 treatment-related death from GI bleeding was observed. Conclusion: High-dose helical tomotherapy with concurrent full-dose chemotherapy resulted in improved local control and long-term survival in patients with LAPC. Future studies are needed to widen the therapeutic window by minimizing late GI toxicity.

  1. Pancreatic cancer chemoprevention by phytochemicals.

    Science.gov (United States)

    Boreddy, Srinivas Reddy; Srivastava, Sanjay K

    2013-06-28

    Pancreatic cancer is fourth leading cause of cancer-related deaths in the United States of America. In spite of recent advances in the current therapeutic modalities such as surgery, radiation and chemotherapy patients, the average five year survival rate remains still less than 5%. Recently, compounds from natural sources receive ample of attention as anti-cancer agents. Many epidemiological studies published over the past few decades provide a strong correlation between consumption of vegetables, fruits or plant derived products and reduced incidence of cancer. The present review focuses on the potential antitumor effects of various natural products.

  2. [The epidemiology of pancreatic cancer].

    Science.gov (United States)

    Lakatos, Gábor; Tulassay, Zsolt

    2010-10-31

    Pancreatic cancer is a relatively uncommon tumor, but even with early diagnosis, mortality rates are high, explaining why this form of cancer has now become a common cause of cancer mortality. There are no screening tests for early detection of pancreatic cancer. It is more common in men than women and is predominantly a disease of elderly people. There is wide variation in the incidence of pancreatic cancer around the world, suggesting that environmental factors are important in the pathogenesis. Smoking is the major known risk factor for pancreatic cancer, while dietary factors seem to be less important. Other possible risk factors include chronic pancreatitis, obesity and type 2 diabetes. Numerous inherited germ line mutations are associated with pancreatic cancer. Of these, hereditary pancreatitis confers the greatest risk, while BRCA2 mutations are the commonest inherited disorder. Polymorphisms in genes that control detoxification of environmental carcinogens and metabolic pathways may alter the risk of pancreatic cancer.

  3. Comparative Study of Gemcitabine Plus Cisplatin and Gemcitabine Plus Fluorouracil in the Treatment of Advanced Pancreatic Cancer

    Institute of Scientific and Technical Information of China (English)

    YongqionShu; LiankeLiu; LinxiangLiu; PuwenHuang; KoihuoLu; YongmeiYin

    2004-01-01

    OBJECTIVE To compare the efficacy and toxicity of gemcitabine plus cisplatin and gemcitabine plus fluorouracil in the treatment of advanced pancreatic cancer. METHODS Sixty patients with advanced pancreatic cancer were randomly divided into a GP group (gemcitabine + cisplatin, 30 cases) and a GF group (gemcitabine + fluorouracil, 30 cases). All patients were treated with gemcitabine at a dose of 1,000mg/m2 (diluted in 100ml saline solution over 30 min) once a week for 3 consecutive weeks. The GP Group was followed by 40mg cisplatin via intravenous drip on days 15,16,17. Group GF was followed by 500mg/m2 5-Fu (diluted in 5% glucose-saline (GS) 500ml, intravenously, over 6 hr) every day for five subsequent days.RESULTS In the GP group, eight cases (32.0%) were PR and MR, the median survival time was 8.7 months, the Clinical Beneficial Rate (CBR) was 57.7%, and the CA19-9 decreased by over 50% in 13 vases (48.1%). In the GF group, 11 cases (45.8%) were PR and MR, the survival time was 10.1 months, the CBR was 82.1%, and CA19-9 decreased by over 50% in 15 cases(53.6%). There was a significant difference in the CBR between the two groups (P<0.05). The main toxicities in both groups were leucopenia and thrombocytopenia with no significant difference. CONCLUSIONS The treatment given to either the GP or GF group is a feasible and well-tolerated chemotherapy regimen for treating advanced pancreatic cancer with improved therapeutic efficacy and few side effects. The median survival period is long and the CBR is high, especially with the GF regimen.

  4. Prospective small bowel mucosal assessment immediately after chemoradiotherapy of unresectable locally advanced pancreatic cancer using capsule endoscopy: a case series.

    Science.gov (United States)

    Yamashina, Takeshi; Takada, Ryoji; Uedo, Noriya; Akasaka, Tomofumi; Hanaoka, Noboru; Takeuchi, Yoji; Higashino, Koji; Ioka, Tatsuya; Ishihara, Ryu; Teshima, Teruki; Nishiyama, Kinji; Iishi, Hiroyasu

    2016-01-01

    In this case series, three consecutive patients with unresectable locally advanced pancreatic cancer (ULAPC) underwent capsule endoscopy (CE) before and after chemoradiotherapy (CRT) to evaluate duodenal and jejunal mucosa, and to examine the relationship between CE findings and dose distribution. CE after CRT showed duodenitis and proximal jejunitis in all three patients. The most inflamed region was the third part of the duodenum, and in dose distribution, this was the closest region to the center of irradiation. This case series shows that CE can safely diagnose acute duodenitis and proximal jejunitis caused by CRT for ULAPC, and that dose distribution is possible to predict the degree of duodenal and jejunal mucosal injuries.

  5. Skeletal Muscle Depletion Predicts the Prognosis of Patients with Advanced Pancreatic Cancer Undergoing Palliative Chemotherapy, Independent of Body Mass Index.

    Directory of Open Access Journals (Sweden)

    Younak Choi

    Full Text Available Body composition has emerged as a prognostic factor in cancer patients. We investigated whether sarcopenia at diagnosis and loss of skeletal muscle during palliative chemotherapy were associated with survival in patients with pancreatic cancer.We retrospectively reviewed the clinical outcomes of pancreatic cancer patients receiving palliative chemotherapy between 2003 and 2010. The cross-sectional area of skeletal muscle at L3 by computed tomography was analyzed with Rapidia 3D software. We defined sarcopenia as a skeletal muscle index (SMI< 42.2 cm2/m2 (male and < 33.9 cm2/m2 (female using ROC curve.Among 484 patients, 103 (21.3% patients were sarcopenic at diagnosis. Decrease in SMI during chemotherapy was observed in 156 (60.9% male and 65 (40.6% female patients. Decrease in body mass index (BMI was observed in 149 patients (37.3%, with no gender difference. By multivariate analysis, sarcopenia (P< 0.001, decreasedBMI and SMI during chemotherapy (P = 0.002, P = 0.004, respectively were poor prognostic factors for overall survival (OS. While the OS of male patients was affected with sarcopenia (P< 0.001 and decreased SMI (P = 0.001, the OS of female patients was influenced with overweight at diagnosis (P = 0.006, decreased BMI (P = 0.032 and decreased SMI (P = 0.014. Particularly, while the change of BMI during chemotherapy did not have impact on OS within the patients with maintained SMI (P = 0.750, decrease in SMI was associated with poor OS within the patients with maintained BMI (HR 1.502; P = 0.002.Sarcopenia at diagnosis and depletion of skeletal muscle, independent of BMI change, during chemotherapy were poor prognostic factors in advanced pancreatic cancer.

  6. Patient Derived Cancer Cell Lines in Identifying Molecular Changes in Patients With Previously Untreated Pancreatic Cancer Receiving Gemcitabine Hydrochloride-Based Chemotherapy

    Science.gov (United States)

    2016-10-18

    Pancreatic Ductal Adenocarcinoma; Stage IA Pancreatic Cancer; Stage IB Pancreatic Cancer; Stage IIA Pancreatic Cancer; Stage IIB Pancreatic Cancer; Stage III Pancreatic Cancer; Stage IV Pancreatic Cancer

  7. Anorexia-cachexia syndrome in pancreatic cancer: recent advances and new pharmacological approach.

    Science.gov (United States)

    Ronga, Ilaria; Gallucci, Fernando; Riccardi, Ferdinando; Uomo, Generoso

    2014-03-01

    About 80% of all pancreatic ductal adenocarcinoma patients suffer from a wasting syndrome referred to as the "cancer anorexia-cachexia syndrome" (CACS) characterized by abnormally low weight, weakness and loss of skeletal muscle mass with or without loss of body fat, which directly impacts overall survival, quality of life, and physical activity. The aim of this review was to examine recent findings about CACS' pathophysiology and to describe the current pharmacological approaches. In recent years many efforts were made to improve our knowledge of CACS; currently we know that cachexia arises from a complex and multifactorial interaction between various mechanisms including inflammation, anorexia/malnutrition, alterations of protein and lipid metabolism; consequently its management requires multidisciplinary and multipharmacological approach that should address the different causes underlying this clinical event. On these premises, several drugs have been proposed starting from the first pharmacological treatment based on progestational agents or corticosteroids; most of them are in the preclinical phase, but some have already reached the clinical experimentation stage. In conclusion, to date, there is no standard effective treatment and further studies are needed to unravel the basic mechanisms underlying CACS and to develop newer therapeutic strategies with the hope to improve the quality of life of pancreatic cancer patients.

  8. Treatment for locally advanced pancreatic cancer%局部晚期胰腺癌的治疗进展

    Institute of Scientific and Technical Information of China (English)

    王梦; 杨继元

    2013-01-01

    局部晚期胰腺癌目前治疗的主要手段是放化疗联合姑息性手术的综合治疗,目的在于延长患者生命的同时提高其生活质量.吉西他滨是目前的标准治疗,以其为基础的联合方案的疗效已得到肯定,与靶向药物联合亦有一定的疗效.新的化疗药物和靶向药物的涌现,为局部晚期胰腺癌的治疗提供了更多的途径.%Combined therapy consisting of radiotherapy,chemotherapy and palliative surgery is the primary management for locally advanced pancreatic cancer,with the purpose of prolonging survival and improving life quality.Gemcitabine is the standard chemotherapy at present.Gemcitabine-based combinations show a definite effect,and the combination with targeted drugs also has a certain degree of efficacy.The development of new chemotherapy drugs and targeted drugs provides more ways for the teatment of locally advanced pancreatic cancer.

  9. Efficacy and safety of gemcitabine plus erlotinib for locally advanced or metastatic pancreatic cancer: a systematic review and meta-analysis

    Science.gov (United States)

    Wang, Yuan; Hu, Guo-fang; Zhang, Qian-qian; Tang, Ning; Guo, Jun; Liu, Li-yan; Han, Xiao; Wang, Xia; Wang, Zhe-hai

    2016-01-01

    Background Pancreatic cancer is considered as a chemoresistant neoplasm with extremely dismal prognosis. Gemcitabine is recommended as the standard agent for locally advanced or metastatic pancreatic cancer. A series of trials have been conducted to improve the outcome of advanced pancreatic cancer with other anticancer drugs in combination with gemcitabine. Unfortunately, the designers of the clinical trials failed to improve the poor prognosis of patients with advanced pancreatic cancer. Erlotinib was the first additional drug that improved the overall survival of patients with advanced pancreatic cancer with gemcitabine. We performed this systematic review and meta-analysis to explore the efficacy and safety of the combination of gemcitabine with erlotinib (GemErlo) for patients with advanced pancreatic cancer using the currently available evidence. Methods PubMed/MEDLINE, EMBASE, the Cochrane Library, and relevant abstracts of major conferences were comprehensively searched. Data results on objective response rate, disease control rate, and 1-year survival were pooled by using MetaAnalyst with a random-effects model. Results on progression-free survival and overall survival were only summarized descriptively. Results A total of 24 studies with 1,742 patients with locally advanced or metastatic pancreatic cancer treated with GemErlo were included. Combined objective response rate was 14.4% (95% CI: 11.6%–17.7%), disease control rate was 55.0% (95% CI: 51.5%–58.5%), and 1-year survival rate was 28.5% (95% CI: 24.0%–33.4%). Progression-free survival ranged from 2.63 to 9.6 months, and overall survival varied from 6 to 10 months. As for the toxicity profile, the most common adverse events (AEs) were hematologic reactions, skin rash, and gastrointestinal reactions. Other severe AEs, which had low incidence, included treatment-induced death and interstitial lung disease. Conclusion Our study showed that GemErlo is associated with reasonable activity in treating

  10. Phase 1 Trials in Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Esther Yu

    2014-07-01

    Full Text Available Despite many clinical trials over the last two decades since the approval of gemcitabine, the survival of patients with pancreatic cancer has improved by a few only months. This disappointing reality underlines an urgent need to develop more effective drugs or better combinations. A variety of phase I trials were presented at the annual meeting of ASCO 2014 focusing on locally advanced and metastatic pancreatic cancer. We summarize four abstracts (abstracts #4116, #4123, #4026, #4138.

  11. Phase 1 Trials in Pancreatic Cancer

    OpenAIRE

    Esther Yu; Muhammad Wasif Saif; Kathryn Huber

    2014-01-01

    Despite many clinical trials over the last two decades since the approval of gemcitabine, the survival of patients with pancreatic cancer has improved by a few only months. This disappointing reality underlines an urgent need to develop more effective drugs or better combinations. A variety of phase I trials were presented at the annual meeting of ASCO 2014 focusing on locally advanced and metastatic pancreatic cancer. We summarize four abstracts (abstracts #4116, #4123, #4026, #4138).

  12. A phase I dose-escalation study of lenalidomide in combination with gemcitabine in patients with advanced pancreatic cancer.

    Directory of Open Access Journals (Sweden)

    Gustav J Ullenhag

    Full Text Available Lenalidomide have both immunomodulatory and anti-angiogenic properties which could confer anti-cancer effects. The aim of this study was to assess the feasibility of combining lenalidomide with the standard treatment gemcitabine in pancreatic cancer patients with advanced disease.Eligible patients had locally advanced or metastatic adenocarcinoma of the pancreas. Patients received lenalidomide days 1-21 orally and gemcitabine 1000 mg/m2 intravenously (days 1, 8 and 15, each 28 day cycle. Three cohorts of lenalidomide were examined (Cohort I = 15 mg, Cohort II = 20 mg and Cohort III = 25 mg daily. The maximum tolerated dose (MTD of lenalidomide given in combination with gemcitabine was defined as the highest dose level at which no more than one out of four (25% subjects experiences a dose-limiting toxicity (DLT. Patients should also be able to receive daily low molecular weight heparin (LMWH (e.g. dalteparin 5000 IU s.c. daily as a prophylactic anticoagulant for venous thromboembolic events (VTEs. Twelve patients (n = 4, n = 3 and n = 5 in cohort I, II and III, respectively were enrolled in this study.Median duration of treatment was 11 weeks (range 1-66, and median number of treatment cycles were three (range 1-14. The only DLT was a cardiac failure grade 3 in cohort III. Frequent treatment-related adverse events (AEs (all grades included neutropenia, leucopenia and fatigue (83% each, but there was no febrile neutropenia; thrombocytopenia (75%; dermatological toxicity (75%; diarrhea and nausea (42% each; and neuropathy (42%.This phase I study demonstrates the feasibility of the combination of lenalidomide and gemcitabine as first-line treatment in patients with advanced pancreatic cancer. The tolerability profile demonstrated in the dose escalation schedule of lenalidomide suggests the dosing of lenalidomide to be 25 mg daily on days 1-21 with standard dosing of gemcitabine and merits further evaluation in a phase II trial.ClinicalTrials.gov NCT

  13. Epidermal Growth Factor Receptor in Pancreatic Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Oliveira-Cunha, Melissa, E-mail: melissacunha@doctors.org.uk [Hepatobiliary Surgery Unit, Manchester Royal Infirmary, Oxford Road, Manchester, M13 9WL (United Kingdom); Newman, William G. [Genetic Medicine, MAHSC, University of Manchester, St Mary' s Hospital, Oxford Road, Manchester, M13 9WL (United Kingdom); Siriwardena, Ajith K. [Hepatobiliary Surgery Unit, Manchester Royal Infirmary, Oxford Road, Manchester, M13 9WL (United Kingdom)

    2011-03-24

    Pancreatic cancer is the fourth leading cause of cancer related death. The difficulty in detecting pancreatic cancer at an early stage, aggressiveness and the lack of effective therapy all contribute to the high mortality. Epidermal growth factor receptor (EGFR) is a transmembrane glycoprotein, which is expressed in normal human tissues. It is a member of the tyrosine kinase family of growth factors receptors and is encoded by proto-oncogenes. Several studies have demonstrated that EGFR is over-expressed in pancreatic cancer. Over-expression correlates with more advanced disease, poor survival and the presence of metastases. Therefore, inhibition of the EGFR signaling pathway is an attractive therapeutic target. Although several combinations of EGFR inhibitors with chemotherapy demonstrate inhibition of tumor-induced angiogenesis, tumor cell apoptosis and regression in xenograft models, these benefits remain to be confirmed. Multimodality treatment incorporating EGFR-inhibition is emerging as a novel strategy in the treatment of pancreatic cancer.

  14. Liposomal cisplatin combined with gemcitabine in pretreated advanced pancreatic cancer patients: a phase I-II study.

    Science.gov (United States)

    Stathopoulos, George P; Boulikas, Teni; Vougiouka, Maria; Rigatos, Sotirios K; Stathopoulos, John G

    2006-05-01

    The present trial is a phase I-II study based on a new liposomal cisplatin (lipoplatin). Previous preclinical and clinical data (phase I pharmacokinetics) led to the investigation of a combined treatment modality involving lipoplatin and gemcitabine. The gemcitabine dose was kept standard at 1000 mg/m2 and the lipoplatin dose was escalated from 25 mg/m2 to 125 mg/m2. The treatment was administered to advanced pretreated pancreatic cancer patients who were refractory to previous chemotherapy which included gemcitabine. Lipoplatin at 125 mg/m2 was defined as dose limiting toxicity (DLT) and 100 mg/m2 as the maximum tolerated dose (MTD) in combination with 1000 mg/m2 of gemcitabine. Preliminary objective response rate data showed a partial response in 2/24 patients (8.3%), disease stability in 14 patients (58.3%) for a median duration of 3 months (range 2-7 months) and clinical benefit in 8 patients (33.3%). Liposomal cisplatin is a non-toxic alternative agent to bare cisplatin. In combination with gemcitabine, it has an MTD of 100 mg/m2 and shows promising efficacy in refractory pancreatic cancer.

  15. Weekly paclitaxel, gemcitabine, and external irradiation followed by randomized farnesyl transferase inhibitor R115777 for locally advanced pancreatic cancer

    Directory of Open Access Journals (Sweden)

    Rich TA

    2012-08-01

    Full Text Available Tyvin A Rich,1 Kathryn Winter,2 Howard Safran,3 John P Hoffman,4 Beth Erickson,5 Pramila R Anne,6 Robert J Myerson,7 Vivian JM Cline-Burkhardt,8 Kimberly Perez,3 Christopher Willett91The Cancer Center, University of Virginia Health System West, University of Virginia, Charlottesville, VA, USA; 2RTOG Statistical Center, Philadelphia, PA, USA; 3Brown University, Providence, RI, USA; 4Foxchase Cancer Center, Philadelphia, PA, USA; 5Medical College of Wisconsin, Milwaukee, WI, USA; 6Thomas Jefferson University, Philadelphia, PA, USA; 7Washington University, St Louis, MO, USA; 8Comprehensive Cancer Centers of Nevada, Las Vegas, NV, USA; 9Duke University, Durham, NC, USAPurpose: The Radiation Therapy Oncology Group (RTOG multi-institutional Phase II study 98-12, evaluating paclitaxel and concurrent radiation (RT for locally advanced pancreatic cancer, demonstrated a median survival of 11.3 months and a 1-year survival of 43%. The purpose of the randomized Phase II study by RTOG 0020 was to evaluate the addition of weekly low-dose gemcitabine with concurrent paclitaxel/RT and to evaluate the efficacy and safety of the farnesyl transferase inhibitor R115777 following chemoradiation.Patients and methods: Patients with unresectable, nonmetastatic adenocarcinoma of the pancreas were eligible. Patients in Arm 1 received gemcitabine, 75 mg/m2/week, and paclitaxel, 40 mg/m2/week, for 6 weeks, with 50.4 Gy radiation (CXRT. Patients in Arm 2 received an identical chemoradiation regimen but then received maintenance R115777, 300 mg twice a day for 21 days every 28 days (CXRT+R115777, until disease progression or unacceptable toxicity.Results: One hundred ninety-five patients were entered into this study, and 184 were analyzable. Grade 4 nonhematologic toxicities occurred in less than 5% of CXRT patients. The most common grade 3/4 toxicity from R115777 was myelosuppression; however, grade 3/4 hepatic, metabolic, musculoskeletal, and neurologic toxicities were

  16. Intensity-Modulated and Image-Guided Radiotherapy in Patients with Locally Advanced Inoperable Pancreatic Cancer after Preradiation Chemotherapy

    Directory of Open Access Journals (Sweden)

    M. Sinn

    2014-01-01

    Full Text Available Background. Radiotherapy (RT in patients with pancreatic cancer is still a controversial subject and its benefit in inoperable stages of locally advanced pancreatic cancer (LAPC, even after induction chemotherapy, remains unclear. Modern radiation techniques such as image-guided radiotherapy (IGRT and intensity-modulated radiotherapy (IMRT may improve effectiveness and reduce radiotherapy-related toxicities. Methods. Patients with LAPC who underwent radiotherapy after chemotherapy between 09/2004 and 05/2013 were retrospectively analyzed with regard to preradiation chemotherapy (PRCT, modalities of radiotherapy, and toxicities. Progression-free (PFS and overall survival (OS were estimated by Kaplan-Meier curves. Results. 15 (68% women and 7 men (median age 64 years; range 40–77 were identified. Median duration of PRCT was 11.1 months (range 4.3–33.0. Six patients (27% underwent conventional RT and 16 patients (73% advanced IMRT and IGRT; median dosage was 50.4 (range 9–54 Gray. No grade III or IV toxicities occurred. Median PFS (estimated from the beginning of RT was 5.8 months, 2.6 months in the conventional RT group (conv-RT, and 7.1 months in the IMRT/IGRT group (P=0.029; median OS was 11.0 months, 4.2 months (conv-RT, and 14.0 months (IMRT/IGRT; P=0.141. Median RT-specific PFS for patients with prolonged PRCT > 9 months was 8.5 months compared to 5.6 months for PRCT 9 months group, with 19.0 months compared to 8.5 months in the PRCT  <  9 months group (P=0.049. Conclusions. IGRT and IMRT after PRCT are feasible and effective options for patients with LAPC after prolonged preradiation chemotherapy.

  17. Weekly paclitaxel, gemcitabine, and external irradiation followed by randomized farnesyl transferase inhibitor R115777 for locally advanced pancreatic cancer

    Science.gov (United States)

    Rich, Tyvin A; Winter, Kathryn; Safran, Howard; Hoffman, John P; Erickson, Beth; Anne, Pramila R; Myerson, Robert J; Cline-Burkhardt, Vivian JM; Perez, Kimberly; Willett, Christopher

    2012-01-01

    Purpose The Radiation Therapy Oncology Group (RTOG) multi-institutional Phase II study 98-12, evaluating paclitaxel and concurrent radiation (RT) for locally advanced pancreatic cancer, demonstrated a median survival of 11.3 months and a 1-year survival of 43%. The purpose of the randomized Phase II study by RTOG 0020 was to evaluate the addition of weekly low- dose gemcitabine with concurrent paclitaxel/RT and to evaluate the efficacy and safety of the farnesyl transferase inhibitor R115777 following chemoradiation. Patients and methods Patients with unresectable, nonmetastatic adenocarcinoma of the pancreas were eligible. Patients in Arm 1 received gemcitabine, 75 mg/m2/week, and paclitaxel, 40 mg/m2/week, for 6 weeks, with 50.4 Gy radiation (CXRT). Patients in Arm 2 received an identical chemoradiation regimen but then received maintenance R115777, 300 mg twice a day for 21 days every 28 days (CXRT+R115777), until disease progression or unacceptable toxicity. Results One hundred ninety-five patients were entered into this study, and 184 were analyzable. Grade 4 nonhematologic toxicities occurred in less than 5% of CXRT patients. The most common grade 3/4 toxicity from R115777 was myelosuppression; however, grade 3/4 hepatic, metabolic, musculoskeletal, and neurologic toxicities were also reported. The median survival time was 11.5 months and 8.9 months for the CXRT and CXRT+R115777 arms, respectively. Conclusions The CXRT arm achieved a median survival of almost 1-year, supporting chemoradiation as an important therapeutic modality for locally advanced pancreatic cancer. Maintenance R115777 is not effective and is associated with a broad range of toxicities. These findings provide clinical evidence that inhibition of farnesylation affects many metabolic pathways, underscoring the challenge of developing an effective K-ras inhibitor. PMID:22977306

  18. Diet and Pancreatic Cancer Prevention.

    Science.gov (United States)

    Casari, Ilaria; Falasca, Marco

    2015-11-23

    Pancreatic cancer is without any doubt the malignancy with the poorest prognosis and the lowest survival rate. This highly aggressive disease is rarely diagnosed at an early stage and difficult to treat due to its resistance to radiotherapy and chemotherapy. Therefore, there is an urgent need to clarify the causes responsible for pancreatic cancer and to identify preventive strategies to reduce its incidence in the population. Some circumstances, such as smoking habits, being overweight and diabetes, have been identified as potentially predisposing factors to pancreatic cancer, suggesting that diet might play a role. A diet low in fat and sugars, together with a healthy lifestyle, regular exercise, weight reduction and not smoking, may contribute to prevent pancreatic cancer and many other cancer types. In addition, increasing evidence suggests that some food may have chemo preventive properties. Indeed, a high dietary intake of fresh fruit and vegetables has been shown to reduce the risk of developing pancreatic cancer, and recent epidemiological studies have associated nut consumption with a protective effect against it. Therefore, diet could have an impact on the development of pancreatic cancer and further investigations are needed to assess the potential chemo preventive role of specific foods against this disease. This review summarizes the key evidence for the role of dietary habits and their effect on pancreatic cancer and focuses on possible mechanisms for the association between diet and risk of pancreatic cancer.

  19. Diet and Pancreatic Cancer Prevention

    Directory of Open Access Journals (Sweden)

    Ilaria Casari

    2015-11-01

    Full Text Available Pancreatic cancer is without any doubt the malignancy with the poorest prognosis and the lowest survival rate. This highly aggressive disease is rarely diagnosed at an early stage and difficult to treat due to its resistance to radiotherapy and chemotherapy. Therefore, there is an urgent need to clarify the causes responsible for pancreatic cancer and to identify preventive strategies to reduce its incidence in the population. Some circumstances, such as smoking habits, being overweight and diabetes, have been identified as potentially predisposing factors to pancreatic cancer, suggesting that diet might play a role. A diet low in fat and sugars, together with a healthy lifestyle, regular exercise, weight reduction and not smoking, may contribute to prevent pancreatic cancer and many other cancer types. In addition, increasing evidence suggests that some food may have chemo preventive properties. Indeed, a high dietary intake of fresh fruit and vegetables has been shown to reduce the risk of developing pancreatic cancer, and recent epidemiological studies have associated nut consumption with a protective effect against it. Therefore, diet could have an impact on the development of pancreatic cancer and further investigations are needed to assess the potential chemo preventive role of specific foods against this disease. This review summarizes the key evidence for the role of dietary habits and their effect on pancreatic cancer and focuses on possible mechanisms for the association between diet and risk of pancreatic cancer.

  20. Adjuvant therapy in pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    Paula Ghaneh; John Slavin; Robert Sutton; Mark Hartley; John P Neoptolemos

    2001-01-01

    The outlook for patients with pancreatic cancer has been grim. There have been major advances in the surgical treatment of pancreatic csncer, leading to a drsmatic reduction in post-operative mortality from the development of high volume specialized centres. This stimulated the study of adjuvant and neoadjuvant treatments in pancreatic cancer including chemoradiotherapy and chemotherapy. Initial protocols have been based on the original but rather small GITSG study first reported in 1985. There have been two large European trials totalling over 600 patients (EORTC and ESPAC-1) that do not support the use of chemoradiation as adjuvant therapy. A second major finding from the ESPAC-1 trial (541 patients randomized) was some but not conclusive evidence for a survival benefit associated with chemotherapy. A third major finding from the ESPAC-1 trial was that the quality of life was not affected by the use of adjuvant treatments compared to surgery alone.The ESPAC-3 trial aims to assess the definitive use of adjuvant chemotherapy in a randomized controlled trial of 990 patients.

  1. Molecular and genetic bases of pancreatic cancer.

    Science.gov (United States)

    Vaccaro, Vanja; Gelibter, Alain; Bria, Emilio; Iapicca, Pierluigi; Cappello, Paola; Di Modugno, Francesca; Pino, Maria Simona; Nuzzo, Carmen; Cognetti, Francesco; Novelli, Francesco; Nistico, Paola; Milella, Michele

    2012-06-01

    Pancreatic cancer remains a formidable challenge for oncologists and patients alike. Despite intensive efforts, attempts at improving survival in the past 15 years, particularly in advanced disease, have failed. This is true even with the introduction of molecularly targeted agents, chosen on the basis of their action on pathways that were supposedly important in pancreatic cancer development and progression: indeed, with the notable exception of the epidermal growth factor receptor (EGFR) inhibitor erlotinib, that has provided a minimal survival improvement when added to gemcitabine, other agents targeting EGFR, matrix metallo-proteases, farnesyl transferase, or vascular endothelial growth factor have not succeeded in improving outcomes over standard gemcitabine monotherapy for a variety of different reasons. However, recent developments in the molecular epidemiology of pancreatic cancer and an ever evolving understanding of the molecular mechanisms underlying pancreatic cancer initiation and progression raise renewed hope to find novel, relevant therapeutic targets that could be pursued in the clinical setting. In this review we focus on molecular epidemiology of pancreatic cancer, epithelial-to-mesenchymal transition and its influence on sensitivity to EGFR-targeted approaches, apoptotic pathways, hypoxia-related pathways, developmental pathways (such as the hedgehog and Notch pathways), and proteomic analysis as keys to a better understanding of pancreatic cancer biology and, most importantly, as a source of novel molecular targets to be exploited therapeutically.

  2. Drugs Approved for Pancreatic Cancer

    Science.gov (United States)

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for pancreatic cancer. The list includes generic names, brand names, and common drug combinations, which are shown in capital letters.

  3. Screening for Pancreatic Cancer.

    Science.gov (United States)

    Wada, Keita; Takaori, Kyoichi; Traverso, L William

    2015-10-01

    Neither extended surgery nor extended indication for surgery has improved survival in patients with pancreatic cancer. According to autopsy studies, presumably 90% are metastatic. The only cure is complete removal of the tumor at an early stage before it becomes a systemic disease or becomes invasive. Early detection and screening of individuals at risk is currently under way. This article reviews the evidence and methods for screening, either familial or sporadic. Indication for early-stage surgery and precursors are discussed. Surgeons should be familiar with screening because it may provide patients with a chance for cure by surgical resection.

  4. Adjuvant and neoadjuvant treatment in pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    Marta Herreros-Villanueva; Elizabeth Hijona; Angel Cosme; Luis Bujanda

    2012-01-01

    Pancreatic adenocarcinoma is one of the most aggressive human malignancies,ranking 4th among causes for cancer-related death in the Western world including the United States.Surgical resection offers the only chance of cure,but only 15 to 20 percent of cases are potentially resectable at presentation.Different studies demonstrate and confirm that advanced pancreatic cancer is among the most complex cancers to treat and that these tumors are relatively resistant to chemotherapy and radiotherapy.Currently there is no consensus around the world on what constitutes "standard"adjuvant therapy for pancreatic cancer.This controversy derives from several studies,each fraught with its own limitations.Standards of care also vary somewhat with regard to geography and economy,for instance chemo-radiotherapy followed by chemotherapy or vice versa is considered the optimal therapy in North America while chemotherapy alone is the current standard in Europe.Regardless of the efforts in adjuvant and neoadjuvant improved therapy,the major goal to combat pancreatic cancer is to find diagnostic markers,identifying the disease in a pre-metastatic stage and making a curative treatment accessible to more patients.In this review,authors examined the different therapy options for advanced pancreatic patients in recent years and the future directions in adjuvant and neoadjuvant treatments for these patients.

  5. Pancreatic Metastasis from Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Julian Jacob

    2010-01-01

    Full Text Available The pancreas is an unusual location for metastases from other primary cancers. Rarely, pancreatic metastases from kidney or colorectal cancers have been reported. However, a variety of other cancers may also spread to the pancreas. We report an exceptional case of pancreatic metastasis from prostate cancer. Differences in management between primary and secondary pancreatic tumors make recognition of metastases to the pancreas an objective of first importance. Knowledge of unusual locations for metastatic spread will reduce diagnostic delay and lead to a timely delivery of an appropriate treatment.

  6. 胰腺癌流行病学和病因学研究进展%Advance in understanding the epidemiology and etiology of pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    吕文超; 崔云甫

    2011-01-01

    胰腺癌是一种恶性度极高的消化系统肿瘤,其早期症状隐匿,发现时多已是晚期,手术切除率低,预后差.随着人类生活习惯与饮食结构的改变,胰腺癌的发病率在全球范围内逐年上升.胰腺癌发病是遗传因素和环境因素相互作用的结果,其可能与基因突变、基因多态性、表观遗传等因素引起的遗传易感性提高有关.某些与胰腺癌相关的危险因素诸如吸烟、肥胖、饮酒、慢性胰腺炎、糖尿病等已越来越受到广泛关注.因此,了解胰腺癌流行病学和病因学的发展将有助于更好地认识这种疾病,具有重要的意义.%Pancreatic cancer is a life-threatening digestive system neoplasm with a low rate of surgical resection and poor prognosis. Symptoms of pancreatic cancer are so insidious that it is difficult to identify them at early stage. Due to changes in human lifestyle and diet, the incidence of pancreatic cancer has been increasing worldwide. Both genetic and environmental factors contribute to the pathogenesis of pancreatic cancer. Some hereditary factors, such as genetic mutations, genetic polymorphisms and epi-genetics, have been demonstrated to be related to the development of pancreatic cancer. Many risk factors associated with pancreatic cancer, such as smoking, obesity, alcohol consumption, chronic pancreatitis, and diabetes, have also been identified. Here we review the recent advances in understanding the epidemiology and etiology of pancreatic cancer.

  7. Autoimmune pancreatitis--recent advances.

    Science.gov (United States)

    Novotný, I; Díte, P; Lata, J; Nechutová, H; Kianicka, B

    2010-01-01

    Autoimmune pancreatitis (AIP) is recognized as a distinct clinical entity, identified as a chronic inflammatory process of the pancreas in which the autoimmune mechanism is involved. Clinically and histologically, AIP has two subsets: type 1--lymphoplasmatic sclerosing pancreatitis with abundant infiltration of the pancreas and other affected organs with immunoglobulin G4-positive plasma cells, and type 2--duct centric fibrosis, characterized by granulocyte epithelial lesions in the pancreas without systemic involvement. In the diagnosis of AIP, two diagnostic criterions are used--the HISORt criteria and Asian Diagnostic Criteria. In the differential diagnosis, the pancreatic cancer must be excluded by endosonographically guided pancreatic biopsy. Typical signs of AIP are concomitant disorders in other organs (kidney, liver, biliary tract, salivary glands, colon, retroperitoneum, prostate). Novel clinicopathological entity was proposed as an 'IgG4-related sclerosing disease' (IgG4-RSC). Extensive IgG4-positive plasma cells and T lymphocyte infiltration is a common characteristics of this disease. Recently, IgG4-RSC syndrome was extended to a new entity, characterized by IgG4 hypergammaglobulinemia and IgG4-positive plasma cell infiltration, this being considered an expression of a lymphoproliferative disease, 'IgG4-positive multiorgan lymphoproliferative syndrome'. This syndrome includes Mikulicz's disease, mediastinal fibrosis, autoimmune hypophysitis, and inflammatory pseudotumor--lung, liver, breast. In the therapy of AIP, steroids constitute first-choice treatment. High response to the corticosteroid therapy is an important diagnostic criterion. In the literature, there are no case-control studies that determine if AIP predisposes to pancreatic cancer. Undoubtedly, AIP is currently a hot topic in pancreatology.

  8. Intensified Neoadjuvant Chemotherapy with Nab-Paclitaxel plus Gemcitabine Followed by FOLFIRINOX in a Patient with Locally Advanced Unresectable Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Volker Kunzmann

    2014-09-01

    Full Text Available The prognosis of patients with locally advanced pancreatic cancer can be improved if secondary complete (R0 resection is possible. In patients initially staged as unresectable this may be achieved with neoadjuvant treatment which is usually chemoradiotherapy based. We report the case of a 46-year-old patient with an unresectable, locally advanced pancreatic cancer (pT4 Nx cM0 G2 who was treated with a sequential neoadjuvant chemotherapy regimen consisting of 2 cycles of nab-paclitaxel plus gemcitabine followed by 4 cycles of FOLFIRINOX. Neoadjuvant chemotherapy resulted in secondary resectability (R0 resection. After 2 cycles of nab-paclitaxel plus gemcitabine, the patient already had a complete metabolic remission as measured by integrated fludeoxyglucose (18F positron emission tomography and computerized tomography. After a follow-up of 18 months the patient is alive without progression of disease. We propose to assess the clinical benefit of sequencing the combinations nab-paclitaxel plus gemcitabine and FOLFIRINOX as neoadjuvant therapy for patients with locally advanced and initially unresectable pancreatic cancer in a controlled clinical trial.

  9. Intensified Neoadjuvant Chemotherapy with Nab-Paclitaxel plus Gemcitabine Followed by FOLFIRINOX in a Patient with Locally Advanced Unresectable Pancreatic Cancer

    Science.gov (United States)

    Kunzmann, Volker; Herrmann, Ken; Bluemel, Christina; Kapp, Markus; Hartlapp, Ingo; Steger, Ulrich

    2014-01-01

    The prognosis of patients with locally advanced pancreatic cancer can be improved if secondary complete (R0) resection is possible. In patients initially staged as unresectable this may be achieved with neoadjuvant treatment which is usually chemoradiotherapy based. We report the case of a 46-year-old patient with an unresectable, locally advanced pancreatic cancer (pT4 Nx cM0 G2) who was treated with a sequential neoadjuvant chemotherapy regimen consisting of 2 cycles of nab-paclitaxel plus gemcitabine followed by 4 cycles of FOLFIRINOX. Neoadjuvant chemotherapy resulted in secondary resectability (R0 resection). After 2 cycles of nab-paclitaxel plus gemcitabine, the patient already had a complete metabolic remission as measured by integrated fludeoxyglucose (18F) positron emission tomography and computerized tomography. After a follow-up of 18 months the patient is alive without progression of disease. We propose to assess the clinical benefit of sequencing the combinations nab-paclitaxel plus gemcitabine and FOLFIRINOX as neoadjuvant therapy for patients with locally advanced and initially unresectable pancreatic cancer in a controlled clinical trial. PMID:25408659

  10. Marantic Endocarditis Associated with Pancreatic Cancer: A Case Series

    Directory of Open Access Journals (Sweden)

    Gayle S. Jameson

    2009-04-01

    Full Text Available Marantic endocarditis, otherwise known as nonbacterial thrombotic endocarditis (NBTE, is a well-documented phenomenon due to hypercoagulability from an underlying cause. It has been associated with a variety of inflammatory states including malignancy. Surprisingly, although hypercoagulability is often seen in patients with pancreatic cancer, marantic endocarditis has rarely been reported antemortem in this population. We report three cases of marantic endocarditis in patients with advanced pancreatic cancer. In two instances, the patients’ neurological symptoms preceded the diagnosis of advanced pancreatic cancer. Health care professionals should be alert to the possibility of marantic endocarditis in any patient with cancer, especially pancreatic cancer, who presents with symptoms of neurological dysfunction or an arterial thrombotic event. Prompt diagnosis and treatment with heparin, unfractionated or low molecular weight, may prevent catastrophic CNS events and decrease morbidity in patients with pancreatic cancer and other malignancies.

  11. Optimizing initial chemotherapy for metastatic pancreatic cancer.

    Science.gov (United States)

    Mantripragada, Kalyan C; Safran, Howard

    2016-05-01

    The two combination chemotherapy regimens FOLFIRINOX and gemcitabine plus nab-paclitaxel represent major breakthroughs in the management of metastatic pancreatic cancer. Both regimens showed unprecedented survival advantage in the setting of front-line therapy. However, their application for treatment of patients in the community is challenging because of significant toxicities, thus limiting potential benefits to a narrow population of patients. Modifications to the dose intensity or schedule of those regimens improve their tolerability, while likely retaining survival advantage over single-agent chemotherapy. Newer strategies to optimize these two active regimens in advanced pancreatic cancer are being explored that can help personalize treatment to individual patients.

  12. A Multicenter Phase II Trial of S-1 With Concurrent Radiation Therapy for Locally Advanced Pancreatic Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Ikeda, Masafumi, E-mail: masikeda@east.ncc.go.jp [Division of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, Chiba (Japan); Ioka, Tatsuya [Department of Hepatobiliary and Pancreatic Oncology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka (Japan); Ito, Yoshinori [Department of Radiation Oncology, National Cancer Center Hospital, Tokyo (Japan); Yonemoto, Naohiro [Department of Epidemiology and Biostatistics, Translational Medical Center, National Center of Neurology and Psychiatry, Tokyo (Japan); Nagase, Michitaka [Department of Clinical Oncology, Jichi Medical University, Tochigi (Japan); Yamao, Kenji [Department of Gastroenterology, Aichi Cancer Center Hospital, Nagoya (Japan); Miyakawa, Hiroyuki [Department of Gastroenterology, Sapporo Kosei General Hospital, Sapporo (Japan); Ishii, Hiroshi [Hepatobiliary and Pancreatic Division, Cancer Institute Hospital, Tokyo (Japan); Furuse, Junji [Department of Internal Medicine, Medical Oncology School of Medicine, Kyorin University, Tokyo (Japan); Sato, Keiko [Kyoto Unit Center, Japan Environment and Children' s Study, Kyoto University Graduate School of Medicine, Kyoto (Japan); Sato, Tosiya [Department of Biostatistics, Kyoto University School of Public Health, Kyoto (Japan); Okusaka, Takuji [Hepatobiliary and Pancreatic Oncology Division, National Cancer Center Hospital, Tokyo (Japan)

    2013-01-01

    Purpose: The aim of this trial was to evaluate the efficacy and toxicity of S-1 and concurrent radiation therapy for locally advanced pancreatic cancer (PC). Methods and Materials: Locally advanced PC patients with histologically or cytologically confirmed adenocarcinoma or adenosquamous carcinoma, who had no previous therapy were enrolled. Radiation therapy was delivered through 3 or more fields at a total dose of 50.4 Gy in 28 fractions over 5.5 weeks. S-1 was administered orally at a dose of 80 mg/m{sup 2} twice daily on the day of irradiation during radiation therapy. After a 2- to 8-week break, patients received a maintenance dose of S-1 (80 mg/m{sup 2}/day for 28 consecutive days, followed by a 14-day rest period) was then administered until the appearance of disease progression or unacceptable toxicity. The primary efficacy endpoint was survival, and the secondary efficacy endpoints were progression-free survival, response rate, and serum carbohydrate antigen 19-9 (CA19-9) response; the safety endpoint was toxicity. Results: Of the 60 evaluable patients, 16 patients achieved a partial response (27%; 95% confidence interval [CI], 16%-40%). The median progression-free survival period, overall survival period, and 1-year survival rate of the evaluable patients were 9.7 months (95% CI, 6.9-11.6 months), 16.2 months (95% CI, 13.5-21.3 months), and 72% (95%CI, 59%-82%), respectively. Of the 42 patients with a pretreatment serum CA19-9 level of {>=}100 U/ml, 34 (81%) patients showed a decrease of greater than 50%. Leukopenia (6 patients, 10%) and anorexia (4 patients, 7%) were the major grade 3-4 toxicities with chemoradiation therapy. Conclusions: The effect of S-1 with concurrent radiation therapy in patients with locally advanced PC was found to be very favorable, with only mild toxicity.

  13. Having Your Cake and Eating It Too: Combining SBRT and Multi-agent Chemotherapy in Locally Advanced Pancreatic Cancer.

    Science.gov (United States)

    Kishan, Amar; Lee, Percy

    2016-01-01

    We read with great interest the results of the LAP07 study comparing capecitabine-based chemoradiation with gemcitabine-based therapy for non-progressive locally advanced pancreatic cancer (LAPC), following four months of gemcitabine-based therapy. The results, consistent with previous data, showed that standard chemoradiation improves local control (LC) but not overall survival. In this brief editorial, we emphasize that LC may still be very important in LAPC, as up to 30% of patients with LAPC may die from locally progressive disease. This is particularly likely to be true as systemic therapies continue to improve in efficacy. We very briefly review the data in support of stereotactic body radiotherapy (SBRT) for LAPC, which has been shown to offer excellent LC with minimal late grade ≥ 2 toxicity rate in a recent multi-institutional phase II study. We underscore that  a short course of SBRT offers an expeditious alternative to a long course of chemoradiation, allowing the use of fully-intensive systemic therapy.

  14. Genetic alterations in pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    Muhammad Wasif Saif; Lena Karapanagiotou; Kostas Syrigos

    2007-01-01

    The diagnosis of pancreatic cancer is devastating for patients and their relatives as the incidence rate is approximately the same as mortality rate. Only a small percentage, which ranges from 0.4% to 4% of patients who have been given this diagnosis, will be alive at five years. At the time of diagnosis, 80% of pancreatic cancer patients have unresectable or metastatic disease.Moreover, the therapeutic alternatives offered by chemotherapy or radiotherapy are few, if not zero. For all these reasons, there is an imperative need of analyzing and understanding the primitive lesions that lead to invasive pancreatic adenocarcinoma. Molecular pathology of these lesions is the key of our understanding of the mechanisms underlying the development of this cancer and will probably help us in earlier diagnosis and better therapeutic results. This review focuses on medical research on pancreatic cancer models and the underlying genetic alterations.

  15. Concurrent radiotherapy with oral fluoropyrimidine versus gemcitabine in locally advanced pancreatic cancer: a systematic review and meta-analysis

    Directory of Open Access Journals (Sweden)

    Yang YF

    2015-11-01

    Full Text Available Yong-Feng Yang,1 Xiao-Hui Cao,1 Chao-En Bao,1 Xin Wan2 1Department of Radiation Oncology, Third Hospital of Hebei Medical University, Shijiazhuang, People’s Republic of China; 2Department of Radiation Oncology, Fourth Hospital of Hebei Medical University, Shijiazhuang, People’s Republic of China Background: Gemcitabine (GEM is the most widely utilized systemic agent in combination with radiation therapy (RT for treating locally advanced pancreatic cancer (LAPC in the concurrent setting. Despite recent interest in using two novel oral fluoropyrimidines (FUs, capecitabine and S-1, in this setting, there is a lack of randomized controlled trials (RCTs to support this approach.Methods: Trials published between 1994 and 2014 were identified by an electronic search of public databases (Medline, Embase, and the Cochrane Library. All prospective studies were independently identified by two authors for inclusion. Demographic data, treatment response, objective response rate (ORR, progression-free and overall survival (PFS and OS, respectively, and toxicities were extracted and analyzed using comprehensive meta-analysis software (version 2.0.Results: Twenty-three cohorts with 843 patients were included: 497 patients were treated with GEM and 346 patients were treated with oral FU. Pooled OS was significantly higher at 1 and 2 years for S-1 plus RT than for GEM plus RT (relative risk [RR] 1.27; 95% confidence interval [CI], 1.00–1.65; P=0.03; and RR 1.75; 95% CI, 1.18–2.60, P=0.002, respectively, while 1-year PFS and ORR were not significantly different between S-1 and GEM-based chemoradiotherapy (P=0.37 and P=0.06, respectively. Additionally, comparable efficacy was found between capecitabine and GEM-based chemoradiotherapy in terms of OS, PFS, and ORR. As for grade 3 and 4 acute toxicity, oral FU plus RT significantly reduced the risk of developing hematologic toxicities, nausea, and vomiting when compared to GEM plus RT (P<0.001.Conclusions

  16. Pancreatic cancer chemoradiotherapy.

    Science.gov (United States)

    Brunner, Thomas B; Seufferlein, Thomas

    2016-08-01

    Pancreatic cancer is the most lethal gastrointestinal tumour. Chemotherapy is the mainstay of therapy in the majority of the patients whereas resection is the only chance of cure but only possible in 15-20% of all patients. The integration of radiotherapy into multimodal treatment concepts is heavily investigated. It is now commonly accepted that induction chemotherapy should precede radiotherapy. When fractionated conventionally it should be given as chemoradiotherapy. Recently, stereotactic body radiotherapy emerged as an alternative, but will have to be carefully investigated in clinical trials. This review aims to give an overview of radiotherapeutic strategies with a focus on the latest developments in the field in the context of chemotherapy and surgery.

  17. Prognostic Factors for Survival and Resection in Patients With Initial Nonresectable Locally Advanced Pancreatic Cancer Treated With Chemoradiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Bjerregaard, Jon K., E-mail: jon.bjerregaard@ouh.regionsyddanmark.dk [Department of Oncology, Odense University Hospital, Odense (Denmark); Institute of Clinical Research, University of Southern Denmark, Odense (Denmark); Mortensen, Michael B. [Department of Surgery, Odense University Hospital, Odense (Denmark); Jensen, Helle A.; Nielsen, Morten [Department of Oncology, Odense University Hospital, Odense (Denmark); Pfeiffer, Per [Department of Oncology, Odense University Hospital, Odense (Denmark); Institute of Clinical Research, University of Southern Denmark, Odense (Denmark)

    2012-07-01

    Background and Purpose: Controversies regarding the optimal therapy for patients with locally advanced pancreatic cancer (LAPC) exist. Although the prognosis as a whole remains dismal, subgroups are known to benefit from intensive therapy, including chemoradiotherapy (CRT). We describe the results in 178 patients treated from 2001 to 2010 and have developed a prognostic model for both survival and the possibility of a subsequent resection in these patients. Methods and Materials: From 2001 until 2010, 178 consecutive patients with LAPC were treated and included in the present study, with CRT consisting of 50 Gy in 27 fractions combined with tegafur-uracil(UFT)/folinic acid(FA). Results: The median survival from diagnosis was 11.5 months. Adverse events of Grade 3 or above were seen in 36% of the patients. Ninety-three percent of the patients completed all fractions. A Cox regression model for survival demonstrated resection (hazard ratio [HR] 0.12; 95% confidence interval [CI], 0.1-0.3) and pre-CRT gemcitabine-based therapy (HR 0.57; 95% CI, 0.4-0.9) as being associated with a favorable outcome, increasing gross tumor volume (HR 1.14; 95% CI, 1.0-1.3) was associated with shorter survival. A logistic regression model showed Stage III disease (odds ratio [OR] 0.16; 95% CI, 0.0-1.1) and abnormal hemoglobin (OR 0.26; 95% CI, 0.0-1.2) as being associated with lower odds of resection. Conclusion: This study confirms the favorable prognosis for patients receiving gemcitabine therapy before CRT and the poor prognosis associated with increasing tumor volume. In addition, CRT in patients with abnormal hemoglobin and Stage III disease rarely induced tumor shrinkage allowing subsequent resection.

  18. Feasibility of Electromagnetic Transponder Use to Monitor Inter- and Intrafractional Motion in Locally Advanced Pancreatic Cancer Patients

    Energy Technology Data Exchange (ETDEWEB)

    Shinohara, Eric T., E-mail: eric.t.shinohara@vanderbilt.edu [Department of Radiation Oncology, The Vanderbilt Clinic, Nashville, TN (United States); Kassaee, Alireza [Department of Radiation Oncology, University of Pennsylvania, Philadelphia, PA (United States); Mitra, Nandita [Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, PA (United States); Vapiwala, Neha; Plastaras, John P. [Department of Radiation Oncology, University of Pennsylvania, Philadelphia, PA (United States); Drebin, Jeff [Department of Surgery, University of Pennsylvania, Philadelphia, PA (United States); Wan, Fei [Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, PA (United States); Metz, James M. [Department of Radiation Oncology, University of Pennsylvania, Philadelphia, PA (United States)

    2012-06-01

    Purpose: The primary objective of this study was to determine the feasibility of electromagnetic transponder implantation in patients with locally advanced unresectable pancreatic cancer. Secondarily, the use of transponders to monitor inter- and intrafractional motion, and the efficacy of breath holding for limiting target motion, were examined. Methods and Materials: During routine screening laparoscopy, 5 patients without metastatic disease were implanted with transponders peri-tumorally. The Calypso System's localization and tracking modes were used to monitor inter- and intrafractional motion, respectively. Intrafractional motion, with and without breath holding, was also examined using Calypso tracking mode. Results: Transponder implantation was well tolerated in all patients, with minimal migration, aside from 1 patient who expulsed a single transponder. Interfractional motion based on mean shifts from setup using tattoos/orthogonal imaging to transponder based localization from 164 treatments was significant in all dimensions. Mean shift (in millimeters), followed by the standard deviation and p value, were as follows: X-axis: 4.5 mm (1.0, p = 0.01); Y axis: 6.4 mm (1.9, p = 0.03); and Z-axis 3.9 mm (0.6, p = 0.002). Mean intrafractional motion was also found to be significant in all directions: superior, 7.2 mm (0.9, p = 0.01); inferior, 11.9 mm (0.9, p < 0.01); anterior: 4.9 mm (0.5, p = 0.01); posterior, 2.9 mm (0.5, p = 0.02); left, 2.2 mm (0.4, p = 0.02); and right, 3.1 mm (0.6, p = 0.04). Breath holding during treatment significantly decreased tumor motion in all directions. Conclusions: Electromagnetic transponder implantation appears to be safe and effective for monitoring inter- and intrafractional motion. Based on these results a larger clinical trial is underway.

  19. Listeria Vaccines for Pancreatic Cancer

    Science.gov (United States)

    2013-10-01

    Immunol 20, 77 (Jan, 2013). 13. S. K. Biswas, C. E. Lewis, J Leukoc Biol 88, 877 (Nov, 2010). 14. L. J. Bayne et al., Cancer Cell 21, 822 (Jun 12, 2012...EMT and dissemination precede prancreatic tumor formation. Cell. 2012; 148:349. 14. Bayne , L.J., Beatty, G.L., Jhala, N., Clark, C.E., Rhim, A.D...immunity in pancreatic cancer. Cancer Cell. 2012; 21:822. 15. Vonderheide, RH, Bajor, DL, Bayne , LJ, and G.L. Beatty. CD40 immunotherapy for pancreatic

  20. Genetic factors affecting patient responses to pancreatic cancer treatment

    Science.gov (United States)

    Fotopoulos, George; Syrigos, Konstantinos; Saif, Muhammad Wasif

    2016-01-01

    Cancer of the exocrine pancreas is a malignancy with a high lethal rate. Surgical resection is the only possible curative mode of treatment. Metastatic pancreatic cancer is incurable with modest results from the current treatment options. New genomic information could prove treatment efficacy. An independent review of PubMed and ScienceDirect databases was performed up to March 2016, using combinations of terms such pancreatic exocrine cancer, chemotherapy, genomic profile, pancreatic cancer pharmacogenomics, genomics, molecular pancreatic pathogenesis, and targeted therapy. Recent genetic studies have identified new markers and therapeutic targets. Our current knowledge of pancreatic cancer genetics must be further advanced to elucidate the molecular basis and pathogenesis of the disease, improve the accuracy of diagnosis, and guide tailor-made therapies. PMID:27708512

  1. Pancreatic Cancer Risk Prediction Models

    Science.gov (United States)

    Developing statistical models that estimate the probability of developing pancreatic cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

  2. Small molecule tyrosine kinase inhibitors in pancreatic cancer

    Directory of Open Access Journals (Sweden)

    Sachin Gupta

    2008-10-01

    Full Text Available Sachin Gupta, Bassel F El-RayesDepartment of Hematology/Oncology, Karmanos Cancer Institute, Wayne State University, MI, USAAbstract: Pancreatic cancer has proven to be chemo-resistant, with gemcitabine being the only cytotoxic agent approved for advanced pancreatic cancer since 1996. Tyrosine kinase inhibitors represent a newer generation of chemotherapeutic agents targeting specific tumor pathways associated with carcinogenesis including cell cycle control, signal transduction, apoptosis and angiogenesis. These agents present a more selective way of treating pancreatic cancer. Erlotinib is the prototype of the tyrosine kinase inhibitors with proven efficacy in advanced pancreatic cancer and has been recently approved in that setting. Multiple other tyrosine kinase inhibitors targeting the VEGFR, PDGFR, and Src kinases are in various phases of clinical trials testing. The preliminary results of these trials have been disappointing. Current challenges in pancreatic cancer clinical trials testing include improving patient selection, identifying effective combinations, improving the predictive value of current preclinical models and better study designs. This review summarizes the present clinical development of tyrosine kinase inhibitors in pancreatic cancer and strategies for future drug development.Keywords: pancreatic cancer, erlotinib, tyrosine kinase inhibitors

  3. Chronic pancreatitis and pancreatic cancer; the clinical aspects and treatment of pancreatic exocrine insufficiency

    NARCIS (Netherlands)

    E.C.M. Sikkens (Edmée)

    2013-01-01

    textabstractIn exocrine pancreatic insufficiency, the pancreas is unable to deliver a sufficient quantity of pancreatic enzymes to the small intestine to digest food. It may occur in several life threatening diseases, including chronic pancreatitis and pancreatic cancer. Due to this lack or absence

  4. Concurrent chemoradiotherapy for advanced pancreatic cancer. 1,000 mg/m{sup 2} gemcitabine can be administered using limited-field radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Yamazaki, Hideya [Osaka Medical Center for Cancer and Cardiovascular Disease, Osaka (Japan). Dept. of Radiation Oncology; National Hospital Organization, Osaka National Hospital, Osaka (Japan). Dept. of Radiology; Nishiyama, Kinji; Koizumi, Masahiko; Tanaka, Eiichi [Osaka Medical Center for Cancer and Cardiovascular Disease, Osaka (Japan). Dept. of Radiation Oncology; Ioka, Tatsuya; Uehara, Hiroyuki; Iishi, Hiroyasu; Nakaizumi, Akihiko [Osaka Medical Center for Cancer and Cardiovascular Disease, Osaka (Japan). Dept. of Internal Medicine; Ohigashi, Hiroaki; Ishikawa, Osamu [Osaka Medical Center for Cancer and Cardiovascular Disease, Osaka (Japan). Dept. of Surgery

    2007-06-15

    Purpose: To examine the feasibility of concurrent use of full-dose gemcitabine (GEM) and radiotherapy for advanced pancreatic cancer. Patient and Methods: 22 patients with advanced pancreatic cancer were subjected to concurrent chemoradiotherapy (GEM 1,000 mg/m2 weekly, three times during 4 weeks). They received limited-field irradiation by three-dimensional radiotherapy planning. Results: Of the 22 patients, 16 (72%) completed the treatment (50 Gy irradiation and at least three times concurrent administration of 1 g/m{sup 2} GEM). One patient with unresectable tail cancer showed peritonitis carcinomatosa and both chemotherapy and radiotherapy had to be stopped. Dose reduction or omission of GEM was necessary in another four patients. In addition, radiotherapy was discontinued in one patient for fatigue. Grade 3 hematologic toxicity was detected in eight patients (36%), and grade 3 nonhematologic toxicity (anorexia) in one patient (5%). In total, the response rate amounted to 32% (seven partial responses), and the median survival time (MST) was 16 months. Among the twelve patients who received preoperative chemoradiotherapy, nine underwent surgery and showed a survival rate of 78% at 1 year. Another 13 patients without surgery showed 14 months of MST. No regional lymph node failure has appeared so far. Conclusion: Limited-field radiotherapy enables the safe concurrent administration of 1,000 mg/m{sup 2} GEM.

  5. Pancreatic Cancer: Are We Moving Forward Yet?

    OpenAIRE

    Muhammad Wasif Saif

    2007-01-01

    Survival for patients with pancreatic cancer remains abysmal. Standard treatment for resected and locally advanced disease usually consists of 5-fluorouracil (5-FU, either bolus or continuous infusion) and external beam radiation. However, recent studies have shown the role of gemcitabine either used alone or incorporated with 5-FU and external beam radiation in this setting. Gemcitabine and erlotinib (Tarceva®) are currently the only standard chemotherapeutic agents approved by FDA for the t...

  6. Proteome-based biomarkers in pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    Chen Sun; Ann H Rosendahl; Daniel Ansari; Roland Andersson

    2011-01-01

    Pancreatic cancer, as a highly malignant cancer and the fourth cause of cancer-related death in world, is characterized by dismal prognosis, due to rapid disease progression, highly invasive tumour phenotype, and resistance to chemotherapy. Despite significant advances in treatment of the disease during the past decade,the survival rate is little improved. A contributory factor to the poor outcome is the lack of appropriate sensitive and specific biomarkers for early diagnosis. Furthermore, biomarkers for targeting, directing and assessing therapeutic intervention, as well as for detection of residual or recurrent cancer are also needed. Thus, the identification of adequate biomarkers in pancreatic cancer is of extreme importance. Recently, accompanying the development of proteomic technology and devices, more and more potential biomarkers have appeared and are being reported. In this review, we provide an overview of the role of proteome-based biomarkers in pancreatic cancer, including tissue, serum, juice, urine and cell lines. We also discuss the possible mechanism and prospects in the future. That information hopefully might be helpful for further research in the field.

  7. What Is Pancreatic Cancer?

    Science.gov (United States)

    ... also called 5-HT ) or its precursor, 5-HTP. The treatment and outlook for pancreatic NETs depend ... known as precancers ). Because people are getting imaging tests such as CT scans more often than in ...

  8. Clinical Outcomes of Specific Immunotherapy in Advanced Pancreatic Cancer: A Systematic Review and Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Jiang Chen

    2017-01-01

    Full Text Available Specific immunotherapies, including vaccines with autologous tumor cells and tumor antigen-specific monoclonal antibodies, are important treatments for PC patients. To evaluate the clinical outcomes of PC-specific immunotherapy, we performed a systematic review and meta-analysis of the relevant published clinical trials. The effects of specific immunotherapy were compared with those of nonspecific immunotherapy and the meta-analysis was executed with results regarding the overall survival (OS, immune responses data, and serum cancer markers data. The pooled analysis was performed by using the random-effects model. We found that significantly improved OS was noted for PC patients utilizing specific immunotherapy and an improved immune response was also observed. In conclusion, specific immunotherapy was superior in prolonging the survival time and enhancing immunological responses in PC patients.

  9. Pharmacological Ascorbate Radiosensitizes Pancreatic Cancer.

    Science.gov (United States)

    Du, Juan; Cieslak, John A; Welsh, Jessemae L; Sibenaller, Zita A; Allen, Bryan G; Wagner, Brett A; Kalen, Amanda L; Doskey, Claire M; Strother, Robert K; Button, Anna M; Mott, Sarah L; Smith, Brian; Tsai, Susan; Mezhir, James; Goswami, Prabhat C; Spitz, Douglas R; Buettner, Garry R; Cullen, Joseph J

    2015-08-15

    The toxicity of pharmacologic ascorbate is mediated by the generation of H2O2 via the oxidation of ascorbate. Because pancreatic cancer cells are sensitive to H2O2 generated by ascorbate, they would also be expected to become sensitized to agents that increase oxidative damage such as ionizing radiation. The current study demonstrates that pharmacologic ascorbate enhances the cytotoxic effects of ionizing radiation as seen by decreased cell viability and clonogenic survival in all pancreatic cancer cell lines examined, but not in nontumorigenic pancreatic ductal epithelial cells. Ascorbate radiosensitization was associated with an increase in oxidative stress-induced DNA damage, which was reversed by catalase. In mice with established heterotopic and orthotopic pancreatic tumor xenografts, pharmacologic ascorbate combined with ionizing radiation decreased tumor growth and increased survival, without damaging the gastrointestinal tract or increasing systemic changes in parameters indicative of oxidative stress. Our results demonstrate the potential clinical utility of pharmacologic ascorbate as a radiosensitizer in the treatment of pancreatic cancer.

  10. Genomic alterations in pancreatic cancer and their relevance to therapy

    Institute of Scientific and Technical Information of China (English)

    Erina; Takai; Shinichi; Yachida

    2015-01-01

    Pancreatic cancer is a highly lethal cancer type, for which there are few viable therapeutic options. But, with the advance of sequencing technologies for global genomic analysis, the landscape of genomic alterations in pancreatic cancer is becoming increasingly well understood. In this review, we summarize current knowledge of genomic alterations in 12 core signaling pathways or cellular processes in pancreatic ductal adenocarcinoma, which is the most common type of malignancy in the pancreas, including four commonly mutated genes and many other genes that are mutated at low frequencies. We also describe the potential implications of these genomic alterations for development of novel therapeutic approaches in the context of personalized medicine.

  11. Gemcitabine with a specific conformal 3D 5FU radiochemotherapy technique is safe and effective in the definitive management of locally advanced pancreatic cancer.

    Science.gov (United States)

    Goldstein, D; Van Hazel, G; Walpole, E; Underhill, C; Kotasek, D; Michael, M; Shapiro, J; Davies, T; Reece, W; Harvey, J; Spry, N

    2007-08-20

    The aim of this phase II study was to assess the feasibility and efficacy of a specific three-dimensional conformal radiotherapy technique with concurrent continuous infusion of 5-fluorouracil (CI 5FU) sandwiched between gemcitabine chemotherapy in patients with locally advanced pancreatic cancer. Patients with inoperable cancer in the pancreatic head or body without metastases were given gemcitabine at 1000 mg m(-2) weekly for 3 weeks followed by a 1-week rest and a 6-week period of radiotherapy and concurrent CI 5FU (200 mg m(-2) day(-1)). The defined target volume was treated to 54 Gy in 30 daily fractions of 1.8 Gy. After 4 weeks' rest, gemcitabine treatment was re-initiated for three cycles (days 1, 8, 15, q28). Forty-one patients were enrolled. At the end of radiotherapy, one patient (2.4%) had a complete response and four patients (9.6%) had a partial response; at the end of treatment, three patients (7.3%) had a complete response and two patients (4.9%) had a partial response. Median survival time was 11.7 months, median time to progression was 7.1 months, and median time to failure of local control was 11.9 months. The 1- and 2-year survival rates were 46.3 and 9.8%, respectively. Treatment-related grade 3 and 4 toxicities were reported by 16 (39.0%) and four (9.8%) patients, respectively. Sixteen out of 41 patients did not complete the planned treatment and nine due to disease progression. This approach to treatment of locally advanced pancreatic cancer is safe and promising, with good local control for a substantial proportion of patients, and merits testing in a randomised trial.

  12. Recent advances in immunotherapy for human pancreatic cancer%胰腺癌免疫治疗的研究现状

    Institute of Scientific and Technical Information of China (English)

    吴应冬; 周国雄

    2011-01-01

    Pancreatic cancer is one of the common highly malignant digestive system tumors. It is associated with a high mortality rate because of early metastasis, low resection rate and poor chemora-diotherapy response. Advances in immunology, such as tumor antigen, immunological surveillance, immunological evasion, immunological tolerance, T cell signal transduction, regulation of cytokines and regulatory DCs, down-regulation of co-stimulatory molecules, and tumor mi-croenvironment, have enriched our knowledge and promoted the development of immunother-apy for pancreatic cancer. In this paper, we will review the recent advances in immunotherapy for pancreatic cancer.%胰腺癌是常见的恶性程度较高的消化系肿瘤之一,转移早、手术切除率低、放化疗效果差、死亡率极高.近年来对肿瘤免疫机制的研究有了很大的进展.人们对肿瘤抗原、免疫监视、免疫逃避、免疫耐受、T淋巴细胞信号转导、细胞因子以及抑制性树突状细胞(DCs)的调节、共刺激分子的下调、肿瘤微环境有了一定的认识,推动了胰腺癌免疫治疗的发展,并在实验室和临床应用中取得了较大的进展,本文主要介绍胰腺癌的免疫治疗进展.

  13. Pancreatic Cancer Imaging: Which Method?

    Directory of Open Access Journals (Sweden)

    Santo E

    2004-07-01

    Full Text Available Pancreatic cancer is the 10th most common malignancy and the 4th largest cancer killer in adults. Surgery offers the only chance of curing these patients. Complete surgical resection is associated with a 5-year survival rate of between 20 and 30%. The challenge is how to best select those patients for curative surgery. Early studies demonstrated excellent sensitivity of EUS in detecting pancreatic tumors in comparison to CT. Similarly, EUS showed an 85-94% accuracy rate for T staging and 70-80% accuracy rate for N staging. Later studies report on substantially less TN staging accuracy for EUS. Possible explanations and the problem of vascular involvement assessment by EUS will be provided. Considering the role of EUS in M staging and a comparison between EUS, MRI, and positron emission tomography, scanning will be presented. A diagnostic algorithm for the evaluation of patients with a suspected pancreatic mass will be offered, stressing the pivotal role of EUS.

  14. [Borderline resectable pancreatic cancer - a definition and effective treatment strategy].

    Science.gov (United States)

    Yokoyama, Yukihiro; Ebata, Tomoki; Igami, Tsuyoshi; Sugawara, Gen; Takahashi, Yuh; Kokuryo, Toshio; Tsunoda, Nobuyuki; Fukaya, Masahide; Uehara, Keisuke; Itatsu, Keita; Yoshioka, Yuichiro; Nagino, Masato

    2012-03-01

    The survival benefit of extended surgery for advanced pancreatic cancer has been denied by four randomized controlled trials. However, there still is confusion and conflict over the definition and effective treatment strategy for so-called locally advanced or borderline resectable pancreatic cancer. Although there are a number of reports that showed outcomes of preoperative chemotherapy or chemoradiotherapy for this disease, the definitions and treatment regimens described in these studies vary. Moreover, all of the studies were Phase I / II trials or retrospective analysis, and there is no Phase III trial currently focused on this issue. It is urgently necessary to establish an international consensus on the definition of borderline resectable pancreatic cancer. The usefulness of neoadjuvant treatment for this disease should also be elucidated in future clinical trials. In this review article, we discuss the current understanding and definition of borderline resectable pancreatic cancer, and the value of neoadjuvant treatment strategy for treating it.

  15. Precursor lesions in pancreatic cancer: morphological and molecular pathology.

    Science.gov (United States)

    Scarlett, Christopher J; Salisbury, Elizabeth L; Biankin, Andrew V; Kench, James

    2011-04-01

    Pancreatic cancer has a dismal prognosis and is the fourth most common cause of cancer related death in Western societies. In large part this is due to its typically late presentation, usually as locally advanced or metastatic disease. Identification of the non-invasive precursor lesions to pancreatic cancer raises the possibility of surgical treatment or chemoprevention at an early stage in the evolution of this disease, when more amenable to therapeutic interventions. Precursor lesions to pancreatic ductal adenocarcinoma, in particular pancreatic intraepithelial neoplasia (PanIN), have been recognised under a variety of synonyms for over 50 years. Over the past decade our understanding of the morphology, biological significance and molecular aberrations of these lesions has grown rapidly and there is now a widely accepted progression model integrating the accumulated morphological and molecular observations. Further progress is likely to be accelerated by improved mouse models of pancreatic cancer and by insight into the cancer genome gained by the International Cancer Genome Consortium (ICGC), in which an Australian consortium is leading the pancreatic cancer initiative. This review also outlines the morphological and molecular features of the other two precursors of pancreatic ductal adenocarcinoma, i.e., intraductal papillary mucinous neoplasms and mucinous cystic neoplasms.

  16. Core signaling pathways and new therapeutic targets in pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    YOU Lei; CHEN Ge; ZHAO Yu-pei

    2010-01-01

    Objective Pancreatic cancer is a highly aggressive malignancy that has been resistant to treatment. Advances in cancer genetics have improved our understanding of this disease, but the genetics of pancreatic cancer remain poorly understood. A better understanding of the pathogenic role of specific gene mutations and core signaling pathways would propel the development of more effective treatments. The objective in this review was to highlight recent research that shows promise for new treatments for pancreatic cancer. Data sources All articles cited in this review were mainly searched from PubMed, which were published in English from 1993 to 2009. Study selection Original articles and critical reviews selected were relevant to the molecular mechanisms of pancreatic cancer. Results Dysregulation of core signaling pathways and processes through frequently genetic alterations can explain the major features of pancreatic tumorigenesis. New therapeutic targets based on recent research are emerging that hold promise for the future management of pancreatic cancer. Conclusion New agents used in conjunction with standard radiotherapy and chemotherapy might help to overcome drug resistance by targeting multiple signaling pathways to induce responsiveness of pancreatic cancer cells to death signals.

  17. Pancreatic Cancer: Updates on Translational Research and Future Applications

    Directory of Open Access Journals (Sweden)

    Evangelos G Sarris

    2013-03-01

    Full Text Available Pancreatic cancer is one of the most lethal malignancies with a mortality rate almost equal to its incidence. It is ranked as the fourth leading cause of cancer-related deaths in the United States, and despite intensive basic and clinical research over the last few years, the survival benefit for the majority of patients with pancreatic cancer is still disappointing. Due to the absence of specific symptoms and the lack of early detection tests, pancreatic cancer is usually diagnosed at an advanced inoperrable stage and palliative chemotherapy with the purine analogue gemcitabine in combination with the targeted agent erlotinib, remains the mainstay method in the management of these patients. Therefore, there is an imperative need for new findings in the translational research field with prognostic, predictive and therapeutic value. In this paper we summarize five most interesting research abstracts as presented at the 2013 American Society of Clinical Oncology (ASCO Gastrointestinal Cancers Symposium. In particular, we focus on Abstract #141 which investigates the interaction between liver and pancreatic organ damage in patients with pancreatic cancer and the potential contribution of the patatin-like phospholipase domain containing 3 (PNPLA3 gene variation in pancreatic cancer development and on Abstract #149, in which, the prognostic and predictive role of SWI/SNF complex, a chromatin-remodeling complex, is examined. The key role of pharmacogenomics, in terms of predicting response and resistance to chemotherapy in pancreatic cancer patients, is analyzed in Abstract #142 and the contribution of circulating tumor cell detection in the early diagnosis of pancreatic cancer, allowing the avoidance of more invasive procedures like EUS-FNA, is discussed in Abstract #157. Lastly, in Abstract #164, the diagnostic utility of YKL-40 and IL-6 in pancreatic cancer patients is investigated.

  18. Pain Management in Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Michael Erdek

    2010-12-01

    Full Text Available A majority of pancreatic cancer patients present with pain at the time of diagnosis. Pain management can be challenging in light of the aggressive nature of this cancer. Apart from conventional pharmacotherapy, timely treatment with neurolytic celiac plexus block (NCPB has been shown to be of benefit. NCPB has demonstrated efficacious pain control in high quality studies with analgesic effects lasting one to two months. NCPB has also shown to decrease the requirements of narcotics, and thus decrease opioid related side effects. Another option for the control of moderate to severe pain is intrathecal therapy (IT. Delivery of analgesic medications intrathecally allows for lower dosages of medications and thus reduced toxicity. Both of the above mentioned interventional procedures have been shown to have low complication rates, and be safe and effective. Ultimately, comprehensive pancreatic cancer pain management necessitates understanding of pain mechanisms and delivery of sequential validated therapeutic interventions within a multidisciplinary patient care model.

  19. Somatostatin, somatostatin receptors, and pancreatic cancer.

    Science.gov (United States)

    Li, Min; Fisher, William E; Kim, Hee Joon; Wang, Xiaoping; Brunicardi, Charles F; Chen, Changyi; Yao, Qizhi

    2005-03-01

    Somatostatin may play an important role in the regulation of cancer growth including pancreatic cancer by interaction with somatostatin receptors (SSTRs) on the cell surface. Five SSTRs were cloned, and the function of these SSTRs is addressed in this review. SSTR-2, SSTR-5, and SSTR-1 are thought to play major roles in inhibiting pancreatic cancer growth both in vitro and in vivo. SSTR-3 may be involved in mediating apoptosis, but the role of SSTR-4 is not clear. In most pancreatic cancers, functional SSTRs are absent. Reintroduction of SSTR genes has been shown to inhibit pancreatic cancer growth in cell cultures and animal models.

  20. Molecular Endoscopic Ultrasound for Diagnosis of Pancreatic Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Bournet, Barbara [Department of Gastroenterology, University Hospital Center Rangueil, 1 avenue Jean Poulhès, TSA 50032, 31059 Toulouse Cedex 9 (France); INSERM U1037, University Hospital Center Rangueil, Toulouse (France); Pointreau, Adeline; Delpu, Yannick; Selves, Janick; Torrisani, Jerome [INSERM U1037, University Hospital Center Rangueil, Toulouse (France); Buscail, Louis, E-mail: buscail.l@chu-toulouse.fr [Department of Gastroenterology, University Hospital Center Rangueil, 1 avenue Jean Poulhès, TSA 50032, 31059 Toulouse Cedex 9 (France); INSERM U1037, University Hospital Center Rangueil, Toulouse (France); Cordelier, Pierre [INSERM U1037, University Hospital Center Rangueil, Toulouse (France)

    2011-02-24

    Endoscopic ultrasound-guided fine needle aspiration-biopsy is a safe and effective technique in diagnosing and staging of pancreatic ductal adenocarcinoma. However its predictive negative value does not exceed 50% to 60%. Unfortunately, the majority of pancreatic cancer patients have a metastatic and/or a locally advanced disease (i.e., not eligible for curative resection) which explains the limited access to pancreatic tissue specimens. Endoscopic ultrasound-guided fine needle aspiration-biopsy is the most widely used approach for cytological and histological material sampling in these situations used in up to two thirds of patients with pancreatic cancer. Based on this unique material, we and others developed strategies to improve the differential diagnosis between carcinoma and inflammatory pancreatic lesions by analysis of KRAS oncogene mutation, microRNA expression and methylation, as well as mRNA expression using both qRT-PCR and Low Density Array Taqman analysis. Indeed, differentiating pancreatic cancer from pseudotumoral chronic pancreatitis remains very difficult in current clinical practice, and endoscopic ultrasound-guided fine needle aspiration-biopsy analysis proved to be very helpful. In this review, we will compile the clinical and molecular advantages of using endoscopic ultrasound-guided fine needle aspiration-biopsy in managing pancreatic cancer.

  1. Juzentaihoto Failed to Augment Antigen-Specific Immunity but Prevented Deterioration of Patients’ Conditions in Advanced Pancreatic Cancer under Personalized Peptide Vaccine

    Directory of Open Access Journals (Sweden)

    Shigeru Yutani

    2013-01-01

    Full Text Available Juzentaihoto (JTT is a well-known Japanese herbal medicine, which has been reported to modulate immune responses and enhance antitumor immunity in animal models. However, it is not clear whether JTT has similar effects on humans. In particular, there is little information on the effects of JTT in antigen-specific immunity in cancer patients. Here we conducted a randomized clinical study to investigate whether combined usage of JTT could affect antigen-specific immunity and clinical findings in advanced pancreatic cancer patients undergoing personalized peptide vaccination (PPV, in which HLA-matched vaccine antigens were selected based on the preexisting host immunity. Fifty-seven patients were randomly assigned to receive PPV with (n=28 or without (n=29 JTT. Unexpectedly, JTT did not significantly affect cellular or humoral immune responses specific to the vaccine antigens, which were determined by antigen-specific interferon-γ secretion in T cells and antigen-specific IgG titers in plasma, respectively. Nevertheless, JTT prevented deterioration of patients’ conditions, such as anemia, lymphopenia, hypoalbuminemia, plasma IL-6 elevation, and reduction of performance status, which are frequently observed in advanced cancers. To our knowledge, this is the first clinical study that examined the immunological and clinical effects of JTT in cancer patients undergoing immunotherapy in humans.

  2. Acute pancreatitis in patients with pancreatic cancer

    Science.gov (United States)

    Li, Shaojun; Tian, Bole

    2017-01-01

    Abstract Acute pancreatitis (AP) is a rare manifestation of pancreatic cancer (PC). The relationship between AP and PC remains less distinct. From January 2009 to November 2015, 47consecutive patients with PC who presented with AP were reviewed for this study. Clinical features, clinicopathologic variables, postoperative complications, and follow-up evaluations of patients were documented in detail from our database. In order to identify cutoff threshold time for surgery, receiver operating curve (ROC) was built according to patients with or without postoperative complications. Cumulative rate of survival was calculated by using the Kaplan–Meier method. The study was conducted in accordance with the principles of the Declaration of Helsinki and the guidelines of West China Hospital. This study included 35 men (74.5%) and 12 women (25.5%) (mean age: 52 years), with a median follow-up of 40 months. AP was clinically mild in 45 (95.7%) and severe in 2 (4.3%). The diagnosis of PC was delayed by 2 to 660 days (median 101 days). Thirty-nine (83.0%) cases underwent surgery. Eight (17.0%) cases performed biopsies only. Of 39 patients, radical surgery was performed in 32 (82.1%) cases and palliative in 7 (19.9%) cases. Two (8.0%) patients were needed for vascular resection and reconstruction. Postoperative complications occurred in 12 (30.8%) patients. About 24.5 days was the best cutoff point, with an area under curve (AUC) of 0.727 (P = 0.025, 95% confidence interval: 0.555–0.8999). The survival rate of patients at 1 year was 23.4%. The median survival in patients with vascular resection and reconstruction was 18 months, compared with 10 months in patients without vascular resection (P = 0.042). For the primary stage (T), Tix was identified in 3 patients, the survival of whom were 5, 28, 50 months, respectively. And 2 of them were still alive at the follow-up period. The severity of AP was mainly mild. Surgical intervention after 24.5 days may benefit for

  3. Future Directions in Pancreatic Cancer Therapy

    Directory of Open Access Journals (Sweden)

    David Orchard-Webb

    2015-05-01

    Full Text Available Pancreatic cancer is a major disease burden that is essentially incurable at present. However significant understanding of the molecular basis of pancreatic cancer has been achieved through sequencing. This is allowing the rational design of therapeutics. The purpose of this review is to introduce the molecular basis of pancreatic cancer, explain the current state of molecular therapy and provide examples of the ongoing developments. These include improvements in chemotherapy, small molecule inhibitors, vaccines, immune checkpoint antibodies, and oncolytics.

  4. Biomarkers and Pharmacogenetics in Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Xunhai Xu

    2011-07-01

    Full Text Available Appropriate identification and validation of biomarkers as well as pharmacogenetics are important in formulating patient-oriented, individualized chemotherapy or biological therapy in cancer patients. These markers can be especially valuable in pancreatic cancer, where high mortality and complex disease biology are frequently encountered. Recently, several advances have been made to further our knowledge in this specific area of pancreatic cancer. In the 2011 American Society of Clinical Oncology (ASCO Annual Meeting, researchers have presented several interesting results in biomarkers development: the identifications of 9 single nucleotide polymorphisms (SNPs that is associated with positive efficacy of gemcitabine (Abstract #4022; the introduction of circulating tumor cells as a prognostic markers in pancreatic adenocarcinoma (Abstract #e14657; the re-affirmation of plasma cytidine deaminase (CDA as a positive predictive markers for gemcitabine efficacy, as well as the postulations that CDA*3 as a potential genotype marker to predict gemcitabine responses (Abstract #e14645; and finally the retrospective tumor tissues analysis in the Arbeitsgemeinschaft Internistische Onkologie (AIO trial in an attempt for epidermal growth factor receptor (EGFR pathway biomarker identifications (Abstract #4047

  5. Pancreatic cancer: epidemiology and risk factors.

    Science.gov (United States)

    Krejs, Guenter J

    2010-01-01

    Ductal adenocarcinoma of the pancreas has an incidence of approximately 10 per 100,000 population per year. This number pertains to Europe, North America and parts of South America (Argentina). Men are more often afflicted than women (female:male ratio of about 1:1.5, though reports vary). There has been a very small but steady increase in the incidence over the last 50 years. Unfortunately, numbers for incidence and mortality are still practically identical for this cancer. The peak of incidence is between 60 and 80 years of age. In absolute numbers, there are 8,000 cases diagnosed annually in Germany, and 33,000 in the US. Pancreatic cancer at pancreatic cancer include high-fat diet, smoking, chronic pancreatitis, primary sclerosing cholangitis, hereditary pancreatitis, family history of pancreatic cancer and diabetes mellitus. In chronic pancreatitis, the risk for pancreatic cancer is increased 20-fold, in hereditary pancreatitis it is 60-fold higher than in the general population. In a kindred with 2 first-degree relatives with pancreatic cancer, the risk for pancreatic cancer for other members of that kindred is 7-fold higher.

  6. Advances in Management of Acute Pancreatitis.

    Science.gov (United States)

    Janisch, Nigeen H; Gardner, Timothy B

    2016-03-01

    This article reviews advances in the management of acute pancreatitis. Medical treatment has been primarily supportive for this diagnosis, and despite extensive research efforts, there are no pharmacologic therapies that improve prognosis. The current mainstay of management, notwithstanding the ongoing debate regarding the volume, fluid type, and rate of administration, is aggressive intravenous fluid resuscitation. Although antibiotics were used consistently for prophylaxis in severe acute pancreatitis to prevent infection, they are no longer used unless infection is documented. Enteral nutrition, especially in patients with severe acute pancreatitis, is considered a cornerstone in management of this disease.

  7. Resveratrol induces apoptosis in pancreatic cancer cells

    Institute of Scientific and Technical Information of China (English)

    ZHOU Jia-hua; CHENG Hai-yan; YU Ze-qian; HE Dao-wei; PAN Zheng; YANG De-tong

    2011-01-01

    Background Pancreatic cancer is one of the most lethal human cancers with a very low survival rate of 5 years.Conventional cancer treatments including surgery, radiation, chemotherapy or combinations of these show little effect on this disease. Several proteins have been proved critical to the development and the progression of pancreatic cancer.The aim of this study was to investigate the effect of resveratrol on apoptosis in pancreatic cancer cells.Methods Several pancreatic cancer cell lines were screened by resveratrol, and its toxicity was tested by normal pancreatic cells. Western blotting was then performed to analyze the molecular mechanism of resveratrol induced apoptosis of pancreatic cancer cell lines.Results In the screened pancreatic cancer cell lines, capan-2 and colo357 showed high sensitivity to resveratrol induced apoptosis. Resveratrol exhibited insignificant toxicity to normal pancreatic cells. In resveratrol sensitive cells,capan-2 and colo357, the activation of caspase-3 was detected and showed significant caspase-3 activation upon resveratrol treatment; p53 and p21 were also detected up-regulated upon resveratrol treatment.Conclusion Resveratrol provides a promising anti-tumor stratagy to fight against pancreatic cancer.

  8. Epidemiology and prevention of pancreatic cancer.

    Science.gov (United States)

    Lowenfels, Albert B; Maisonneuve, Patrick

    2004-05-01

    Pancreatic cancer is an uncommon tumor, but because the mortality rate approaches 100%, this form of cancer has now become a common cause of cancer mortality. In the United States it is the fourth most frequent cause of cancer mortality; in Japan it ranks as the fifth commonest cause of death from cancer. Smoking is the major known risk factor for pancreatic cancer, accounting for approximately 25-30% of all cases. Some of the time-dependent changes in the frequency of pancreatic cancer can be explained by smoking trends. Aggressive public health measures to control smoking would substantially reduce the burden of pancreatic cancer. Dietary factors are less important for pancreatic cancer than for other digestive tract tumors, but consumption of a diet with adequate quantities of fruits and vegetables, plus control of calories either by dietary measures or by exercise will help to prevent this lethal tumor. There are more than a dozen inherited germline mutations that increase the risk of pancreatic cancer. Of these, hereditary pancreatitis confers the greatest risk, while BRCA2 mutations are the commonest inherited disorder. In addition to germline defects, there are several common polymorphisms in genes that control detoxification of environmental carcinogens that may alter the risk of pancreatic cancer. More research will be needed in this area, to explain and to clarify the interaction between genes and environmental factors.

  9. Pancreatic cancer: systemic combination therapies for a heterogeneous disease.

    Science.gov (United States)

    Melisi, Davide; Calvetti, Lorenzo; Frizziero, Melissa; Tortora, Giampaolo

    2014-01-01

    Pancreatic cancer is the only human malignancy for which patients' survival has not improved substantially during the past 30 years. Despite advances in the comprehension of the molecular mechanisms underlying pancreatic carcinogenesis, current systemic treatments offer only a modest benefit in tumor-related symptoms and survival. Over the past decades, gemcitabine and its combination with other standard cytotoxic agents have been the reference treatments for advanced pancreatic cancer patients. The recent introduction of the three-drug combination regimen FOLFIRINOX or the new taxane nab-paclitaxel represent key advances for a better control of the disease. Novel agents targeting molecular mechanisms involved in cancer development and maintenance are currently under clinical investigation. This review describes the most important findings in the field of systemic combination therapies for the treatment of pancreatic cancer. We discuss the emerging evidences for the clinical activity of combination treatments with standard chemotherapy plus novel agents targeting tumor cell-autonomous and tumor microenvironment signaling pathways. We present some of the most important advances in the comprehension of the molecular mechanisms responsible for the chemoresistance of pancreatic cancer and the emerging therapeutic targets to overcome this resistance.

  10. ADH-1, Gemcitabine Hydrochloride and Cisplatin in Treating Patients With Metastatic Pancreatic or Biliary Tract Cancer That Cannot Be Removed By Surgery

    Science.gov (United States)

    2013-05-07

    Acinar Cell Adenocarcinoma of the Pancreas; Adenocarcinoma of the Gallbladder; Adult Primary Cholangiocellular Carcinoma; Advanced Adult Primary Liver Cancer; Cholangiocarcinoma of the Gallbladder; Duct Cell Adenocarcinoma of the Pancreas; Localized Unresectable Adult Primary Liver Cancer; Periampullary Adenocarcinoma; Recurrent Adult Primary Liver Cancer; Recurrent Gallbladder Cancer; Recurrent Pancreatic Cancer; Stage II Gallbladder Cancer; Stage III Pancreatic Cancer; Stage IIIA Gallbladder Cancer; Stage IIIB Gallbladder Cancer; Stage IV Pancreatic Cancer; Stage IVA Gallbladder Cancer; Stage IVB Gallbladder Cancer

  11. Translating discovery in zebrafish pancreatic development to human pancreatic cancer: biomarkers, targets, pathogenesis, and therapeutics.

    Science.gov (United States)

    Yee, Nelson S; Kazi, Abid A; Yee, Rosemary K

    2013-06-01

    Abstract Experimental studies in the zebrafish have greatly facilitated understanding of genetic regulation of the early developmental events in the pancreas. Various approaches using forward and reverse genetics, chemical genetics, and transgenesis in zebrafish have demonstrated generally conserved regulatory roles of mammalian genes and discovered novel genetic pathways in exocrine pancreatic development. Accumulating evidence has supported the use of zebrafish as a model of human malignant diseases, including pancreatic cancer. Studies have shown that the genetic regulators of exocrine pancreatic development in zebrafish can be translated into potential clinical biomarkers and therapeutic targets in human pancreatic adenocarcinoma. Transgenic zebrafish expressing oncogenic K-ras and zebrafish tumor xenograft model have emerged as valuable tools for dissecting the pathogenetic mechanisms of pancreatic cancer and for drug discovery and toxicology. Future analysis of the pancreas in zebrafish will continue to advance understanding of the genetic regulation and biological mechanisms during organogenesis. Results of those studies are expected to provide new insights into how aberrant developmental pathways contribute to formation and growth of pancreatic neoplasia, and hopefully generate valid biomarkers and targets as well as effective and safe therapeutics in pancreatic cancer.

  12. Molecular Mechanism Underlying Lymphatic Metastasis in Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Zhiwen Xiao

    2014-01-01

    Full Text Available As the most challenging human malignancies, pancreatic cancer is characterized by its insidious symptoms, low rate of surgical resection, high risk of local invasion, metastasis and recurrence, and overall dismal prognosis. Lymphatic metastasis, above all, is recognized as an early adverse event in progression of pancreatic cancer and has been described to be an independent poor prognostic factor. It should be noted that the occurrence of lymphatic metastasis is not a casual or stochastic but an ineluctable and designed event. Increasing evidences suggest that metastasis-initiating cells (MICs and the microenvironments may act as a double-reed style in this crime. However, the exact mechanisms on how they function synergistically for this dismal clinical course remain largely elusive. Therefore, a better understanding of its molecular and cellular mechanisms involved in pancreatic lymphatic metastasis is urgently required. In this review, we will summarize the latest advances on lymphatic metastasis in pancreatic cancer.

  13. Identification of distinct phenotypes of locally advanced pancreatic adenocarcinoma.

    LENUS (Irish Health Repository)

    Teo, Minyuen

    2013-03-01

    A significant number of pancreatic ductal adenocarcinoma present as locally advanced disease. Optimal treatment remains controversial. We sought to analyze the clinical course of locally advanced pancreatic adenocarcinoma (LAPC) in order to identify potential distinct clinical phenotypes.

  14. Pancreatic cancer: from bench to bedside

    Science.gov (United States)

    Ma, Yaokai; Wu, Qing; Li, Xin; Gu, Xiaoqiang; Xu, Jiahua

    2016-01-01

    Pancreatic cancer is recognized as the king of carcinoma, and the gap between basic research and clinical practice is difficult to improve the treatment effect. Translational medicine builds an important bridge between pancreatic cancer basic research and clinical practice from the pathogenesis, early diagnosis of pancreatic carcinoma, drug screening, treatment strategies and metastasis prediction. This article will carry on the concrete elaboration to the above several aspects.

  15. Proton therapy for pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    Romaine; C; Nichols; Soon; Huh; Zuofeng; Li; Michael; Rutenberg

    2015-01-01

    Radiotherapy is commonly offered to patients with pancreatic malignancies although its ultimate utility is compromised since the pancreas is surrounded by exquisitely radiosensitive normal tissues, such as the duodenum, stomach, jejunum, liver, and kidneys. Proton radiotherapy can be used to create dose distributions that conform to tumor targets with significant normal tissue sparing. Because of this, protons appear to represent a superior modality for radiotherapy delivery to patients with unresectable tumors and those receiving postoperative radiotherapy. A particularly exciting opportunity for protons also exists for patients with resectable and marginally resectable disease. In this paper, we review the current literature on proton therapy for pancreatic cancer and discuss scenarios wherein the improvement in the therapeutic index with protons may have the potential to change the management paradigm for this malignancy.

  16. Pharmacogenomics and Pancreatic Cancer Treatment. Optimizing Current Therapy and Individualizing Future Therapy

    Directory of Open Access Journals (Sweden)

    Soonmo Peter Kang

    2008-05-01

    Full Text Available Each year, more than 30,000 Americans are diagnosed with pancreatic cancer. We have only made incremental advancements in treatment of pancreatic cancer despite our best efforts. Research has revealed that pancreatic cancer is a genetic disease which is associated with various forms of cancer associated genetic alterations. Identification and understanding of these carcinogenic gene alterations is the base upon which we can overcome drug resistance and develop novel treatment approaches. In this paper, we review current understanding of pharmacogenomics of pancreatic cancer treatment and address future direction of the field.

  17. Therapeutic Tools in Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Christopher J Hoimes

    2009-03-01

    Full Text Available Pancreatic cancer is the fourth leading cause of cancer death in the United States and has a lower survival rate than other digestive tract tumors. It remains a therapeutic challenge with limited active agents. Honing our current understanding of markers of toxicity and response, and individualizing treatment with the prognostic and therapeutic tools available are important to make a worthy impact on a patient’s course. The authors summarize selected abstracts from the ASCO Gastrointestinal Cancers Symposium, San Francisco, CA, USA, January 15-17, 2009. The Symposium featured pancreatic cancer in 84 research abstracts, of which, seven are reviewed that focus on markers of toxicity: cytidine deaminase (Abstract #151 and haptogloin (Abstract #167 as markers of gemcitabine toxicity; markers of response: use of PET scan for prognosis (Abstract #157, and correlations with CA 19-9 to postchemo-radiation resectability (Abstract #215 and time to progression (Abstract #160; and individualized applications: characterizing the phenotypic similarities between a patient tumor and the direct xenograft (Abstract #154 and a report about the poor outcome of patients with ascites (Abstract #220. Validated clinical tools that can assist in managing patients through the narrow therapeutic window are needed.

  18. Living as a Pancreatic Cancer Survivor

    Science.gov (United States)

    ... pain Pancreatic cancer often causes weight loss and weakness from poor nutrition. These symptoms might be caused by treatment or by the cancer itself. A team of doctors and nutritionists can work with you ...

  19. Recent Advances in Autoimmune Pancreatitis.

    Science.gov (United States)

    Hart, Phil A; Zen, Yoh; Chari, Suresh T

    2015-07-01

    Autoimmune pancreatitis (AIP) is a form of chronic pancreatitis that is characterized clinically by frequent presentation with obstructive jaundice, histologically by a dense lymphoplasmacytic infiltrate with fibrosis, and therapeutically by a dramatic response to corticosteroid therapy. Two distinct diseases, type 1 and type 2 AIP, share these features. However, these 2 diseases have unique pancreatic histopathologic patterns and differ significantly in their demographic profiles, clinical presentation, and natural history. Recognizing the popular and long-standing association of the term "AIP" with what is now called "type 1 AIP," we suggest using "AIP" solely for type 1 AIP and to acknowledge its own distinct disease status by using "idiopathic duct-centric chronic pancreatitis" (IDCP) for type 2 AIP. AIP is the pancreatic manifestation of immunoglobulin G4-related disease (IgG4-RD). The etiopathogenesis of AIP and IgG4-RD is largely unknown. However, the remarkable effectiveness of B-cell depletion therapy with rituximab in patients with AIP and IgG4-RD highlights the crucial role of B cells in its pathogenesis. IDCP is less commonly recognized, and little is known about its pathogenesis. IDCP has no biomarker but is associated with inflammatory bowel disease in ~25% of patients. Recently, the international consensus diagnostic criteria for AIP identified combinations of features that are diagnostic of both diseases. Both AIP and IDCP are corticosteroid responsive; however, relapses are common in AIP and rare in IDCP. Therefore, maintenance therapy with either an immunomodulator (eg, azathioprine, 6-mercaptopurine, or mycophenolate mofetil) or rituximab is often necessary for patients with AIP. Long-term survival is excellent for both patients with AIP and patients with IDCP.

  20. Current progress in immunotherapy for pancreatic cancer.

    Science.gov (United States)

    Foley, Kelly; Kim, Victoria; Jaffee, Elizabeth; Zheng, Lei

    2016-10-10

    Pancreatic cancer remains one of the most lethal cancers with few treatment options. Immune-based strategies to treat pancreatic cancer, such as immune checkpoint inhibitors, therapeutic vaccines, and combination immunotherapies, are showing promise where other approaches have failed. Immune checkpoint inhibitors, including anti-CTLA4, anti-PD-1, and anti-PD-L1 antibodies, are effective as single agents in immune sensitive cancers like melanoma, but lack efficacy in immune insensitive cancers including pancreatic cancer. However, these inhibitors are showing clinical activity, even in traditionally non-immunogenic cancers, when combined with other interventions, including chemotherapy, radiation therapy, and therapeutic vaccines. Therapeutic vaccines given together with immune modulating agents are of particular interest because vaccines are the most efficient way to induce effective anti-tumor T cell responses, which is required for immunotherapies to be effective. In pancreatic cancer, early studies suggest that vaccines can induce T cells that have the potential to recognize and kill pancreatic cancer cells, but the tumor microenvironment inhibits effective T cell trafficking and function. While progress has been made in the development of immunotherapies for pancreatic cancer over the last several years, additional trials are needed to better understand the signals within the tumor microenvironment that are formidable barriers to T cell infiltration and function. Additionally, as more pancreatic specific antigens are identified, immunotherapies will continue to be refined to provide the most significant clinical benefit.

  1. Regulators of epithelial mesenchymal transition in pancreatic cancer

    Directory of Open Access Journals (Sweden)

    Shin eHamada

    2012-07-01

    Full Text Available Pancreatic cancer is a leading cause of cancer related death due to its invasive nature. Despite the improvement of diagnostic strategy, early diagnosis of pancreatic cancer is still challenging. Surgical resection is the only curative therapy, while vast majority of patients are not eligible for this therapeutic option. Complex biological processes are involved in the establishment of invasion and metastasis of pancreatic cancer and epithelial-mesenchymal transition (EMT has been reported to play crucial role. EMT is part of the normal developmental processes which mobilizes epithelial cells and yields mesenchymal phenotype. Deregulation of EMT inducing molecules in pancreatic cancer is reported, such as multiple cytokines, growth factors and downstream transcriptional factors. In addition to these molecules, non-coding RNA including miRNA also contributes to EMT. EMT of cancer cell also correlates with cancer stem cell properties such as chemoresistance or tumorigenicity, therefore these upstream regulators of EMT could be attractive therapeutic targets and several candidates are examined for clinical application. This review summarizes recent advances in this field, focusing the regulatory molecules of EMT and their downstream targets. Further understanding and research advances will clarify the cryptic mechanism of cancer metastasis and delineate novel therapeutic targets.

  2. Study on chronic pancreatitis and pancreatic cancer using MRS and pancreatic juice samples

    Institute of Scientific and Technical Information of China (English)

    Jian Wang; Chao Ma; Zhuan Liao; Bing Tian; Jian-Ping Lu

    2011-01-01

    AIM: To investigate the markers of pancreatic diseases and provide basic data and experimental methods for the diagnosis of pancreatic diseases. METHODS: There were 15 patients in the present study, among whom 10 had pancreatic cancer and 5, chronic pancreatitis. In all patients, pancreatic cancer or chronic pancreatitis was located on the head of the p-a-ncreas. Pathology data of all pa tients was confirmed by biopsy and surgery. Among the 10 patients with pancreatic cancer, 3 people had a medical history of longterm alcohol consumption. Of 5 patients with chronic pancreatitis, 4 men suffered from alcoholic chronic pancreatitis. Pancreatic juice samples were obtained from patients by endoscopic retrograde cholangiopancreatography. Magnetic resonance spectroscopyn was performed on an 11.7-T scanner (Bruker DRX-500) using Call-Purcell-Meiboom-Gill pulse sequences. The parameters were as follows: spectral width, 15 KHz; time domain, 64 K; number of scans, 512; and acquisition time, 2.128 s. RESULTS: The main component of pancreatic juice included leucine, iso-leucine, valine, lactate, alanine, acetate, aspartate, lysine, glycine, threonine, tyrosine, histidine, tryptophan, and phenylalanine. On performing 1D 1H and 2D total correlation spectroscopy, we found a triplet peak at the chemical shift of 1.19 ppm, which only appeared in the spectra of pancreatic juice obtained from patients with alcoholic chronic pancreatitis. This triplet peak was considered the resonance of the methyl of ethoxy group, which may be associated with the metabolism of alcohol in the pancreas. CONCLUSION: The triplet peak, at the chemical shift of 1.19 ppm is likely to be the characteristic metabolite of alcoholic chronic pancreatitis.

  3. Pancreatic cancer stem cells: fact or fiction?

    Science.gov (United States)

    Bhagwandin, Vikash J; Shay, Jerry W

    2009-04-01

    The terms cancer-initiating or cancer stem cells have been the subject of great interest in recent years. In this review we will use pancreatic cancer as an overall theme to draw parallels with historical findings to compare to recent reports of stem-like characteristics in pancreatic cancer. We will cover such topics as label-retaining cells (side-population), ABC transporter pumps, telomerase, quiescence, cell surface stem cell markers, and epithelial-mesenchymal transitions. Finally we will integrate the available findings into a pancreatic stem cell model that also includes metastatic disease.

  4. Revising You the Staging for Pancreatic Cancer in 2012

    Directory of Open Access Journals (Sweden)

    Muhammad Wasif Saif

    2012-03-01

    Full Text Available In 2010, there were an estimated 43,140 new cases of pancreatic ductal adenocarcinoma and 36,800 deaths from pancreatic cancer in the United States [1]. This represents the 10th most common cancer diagnosis but the 4th most common cause of cancer-related death among men and women (6% of all cancer-related deaths, highlighting the disproportionate mortality associated with this diagnosis [2]. Why is Staging so Important? Sadly, only 20% patients are “resectable” at the time of diagnosis [3]. Pancreatic cancer is “resectable” if the tumor is confined to the pancreas without the encasement of adjacent surrounding major vessels, or distant metastases. Even among those patients who undergo resection for pancreatic cancer and have tumor-free margins, the 5-year survival rate after resection is 10-25% and the median survival is 15-19 months [3]. “Locally advanced pancreatic cancer” is defined as the tumor that has a local invasion: arterial (celiac trunk, hepatic artery, superior mesenteric artery or venous (portal vein, superior mesenteric vein but not metastasized, and represents about 25% of pancreatic cancer cases at presentation [4]. Locally advanced stage is associated with a median survival of 6-10 months. The vast majority of these patients develop metastatic disease within the first year of therapy. The tumor is considered “advanced” when it has metastasized to other organs, such as the liver or distant areas of the abdomen. Approximately 45% to 55% of patients are diagnosed at this stage. The prognosis of patients with advanced disease remains extremely poor, with a median survival of 6 months [5].

  5. Baseline Metabolic Tumor Volume and Total Lesion Glycolysis Are Associated With Survival Outcomes in Patients With Locally Advanced Pancreatic Cancer Receiving Stereotactic Body Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Dholakia, Avani S. [Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Chaudhry, Muhammad; Leal, Jeffrey P. [Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Chang, Daniel T. [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California (United States); Raman, Siva P. [Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Hacker-Prietz, Amy [Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Su, Zheng; Pai, Jonathan [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California (United States); Oteiza, Katharine E.; Griffith, Mary E. [Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Wahl, Richard L. [Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Tryggestad, Erik [Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Pawlik, Timothy [Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Laheru, Daniel A. [Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Wolfgang, Christopher L. [Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Koong, Albert C. [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California (United States); and others

    2014-07-01

    Purpose: Although previous studies have demonstrated the prognostic value of positron emission tomography (PET) parameters in other malignancies, the role of PET in pancreatic cancer has yet to be well established. We analyzed the prognostic utility of PET for patients with locally advanced pancreatic cancer (LAPC) undergoing fractionated stereotactic body radiation therapy (SBRT). Materials and Methods: Thirty-two patients with LAPC in a prospective clinical trial received up to 3 doses of gemcitabine, followed by 33 Gy in 5 fractions of 6.6 Gy, using SBRT. All patients received a baseline PET scan prior to SBRT (pre-SBRT PET). Metabolic tumor volume (MTV), total lesion glycolysis (TLG), and maximum and peak standardized uptake values (SUV{sub max} and SUV{sub peak}) on pre-SBRT PET scans were calculated using custom-designed software. Disease was measured at a threshold based on the liver SUV, using the equation Liver{sub mean} + [2 × Liver{sub sd}]. Median values of PET parameters were used as cutoffs when assessing their prognostic potential through Cox regression analyses. Results: Of the 32 patients, the majority were male (n=19, 59%), 65 years or older (n=21, 66%), and had tumors located in the pancreatic head (n=27, 84%). Twenty-seven patients (84%) received induction gemcitabine prior to SBRT. Median overall survival for the entire cohort was 18.8 months (95% confidence interval [CI], 15.7-22.0). An MTV of 26.8 cm{sup 3} or greater (hazard ratio [HR] 4.46, 95% CI 1.64-5.88, P<.003) and TLG of 70.9 or greater (HR 3.08, 95% CI 1.18-8.02, P<.021) on pre-SBRT PET scan were associated with inferior overall survival on univariate analysis. Both pre-SBRT MTV (HR 5.13, 95% CI 1.19-22.21, P=.029) and TLG (HR 3.34, 95% CI 1.07-10.48, P=.038) remained independently associated with overall survival in separate multivariate analyses. Conclusions: Pre-SBRT MTV and TLG are potential predictive factors for overall survival in patients with LAPC and may assist in

  6. Hypofractionated Image-Guided IMRT in Advanced Pancreatic Cancer With Simultaneous Integrated Boost to Infiltrated Vessels Concomitant With Capecitabine: A Phase I Study

    Energy Technology Data Exchange (ETDEWEB)

    Passoni, Paolo, E-mail: passoni.paolo@hsr.it [Department of Radiation Oncology, San Raffaele Scientific Institute, Milan (Italy); Reni, Michele [Department of Medical Oncology, San Raffaele Scientific Institute, Milan (Italy); Cattaneo, Giovanni M. [Department of Medical Physics, San Raffaele Scientific Institute, Milan (Italy); Slim, Najla [Department of Radiation Oncology, San Raffaele Scientific Institute, Milan (Italy); Cereda, Stefano [Department of Medical Oncology, San Raffaele Scientific Institute, Milan (Italy); Balzano, Gianpaolo; Castoldi, Renato [Department of Surgery, San Raffaele Scientific Institute, Milan (Italy); Longobardi, Barbara [Department of Medical Physics, San Raffaele Scientific Institute, Milan (Italy); Bettinardi, Valentino; Gianolli, Luigi [Department of Nuclear Medicine, San Raffaele Scientific Institute, Milan (Italy); Gusmini, Simone [Department of Radiology, San Raffaele Scientific Institute, Milan (Italy); Staudacher, Carlo [Department of Surgery, San Raffaele Scientific Institute, Milan (Italy); Calandrino, Riccardo [Department of Medical Physics, San Raffaele Scientific Institute, Milan (Italy); Di Muzio, Nadia [Department of Radiation Oncology, San Raffaele Scientific Institute, Milan (Italy)

    2013-12-01

    tumor subvolumes concomitant with capecitabine is feasible in chemotherapy-pretreated patients with advanced pancreatic cancer.

  7. Pancreatic cancer vaccine: a unique potential therapy

    Directory of Open Access Journals (Sweden)

    Cappello P

    2015-12-01

    Full Text Available Paola Cappello, Moitza Principe, Francesco Novelli Department of Molecular Biotechnologies and Health Sciences, Center for Experimental Research and Medical Studies, AOU Città della Salute e della Scienza di Torino, University of Turin, Turin, Italy Abstract: Pancreatic ductal adenocarcinoma (PDA is a lethal disease and is one of the cancers that is most resistant to traditional therapies. Historically, neither chemotherapy nor radiotherapy has provided any significant increase in the survival of patients with PDA. Despite intensive efforts, any attempts to improve the survival in the past 15 years have failed. This holds true even after the introduction of molecularly targeted agents, chosen on the basis of their involvement in pathways that are considered to be important in PDA development and progression. Recently, however, FOLFIRINOX (5-fluorouracil, leucovorin, irinotecan, and oxaliplatin treatment has provided a limited survival advantage in patients with advanced PDA. Therefore, effective therapeutic strategies are urgently needed to improve the survival rate of patients with PDA. Results from the last 10 years of research in the field of PDA have helped to identify new immunological targets and develop new vaccines that are capable of stimulating an immune response. In addition, the information obtained about the role of the tumor microenvironment in suppressing the immune response and the possibility of targeting PDA microenvironment to limit immune suppression and enhance the response of effector T-cells has opened new avenues for treating this incurable disease. The time is ripe for developing new therapeutic approaches that are able to effectively counteract the progression and spreading of PDA. This review discusses the potential prospects in the care of patients with pancreatic cancer through vaccination and its combination therapy with surgery, chemotherapy, targeting of the tumor microenvironment, and inhibition of immunological

  8. New insights into pancreatic cancer stem cells

    Institute of Scientific and Technical Information of China (English)

    Chinthalapally V Rao; Altaf Mohammed

    2015-01-01

    Pancreatic cancer (PC) has been one of the deadliest of allcancers, with almost uniform lethality despite aggressivetreatment. Recently, there have been important advancesin the molecular, pathological and biological understandingof pancreatic cancer. Even after the emergence of recentnew targeted agents and the use of multiple therapeuticcombinations, no treatment option is viable in patients withadvanced cancer. Developing novel strategies to targetprogression of PC is of intense interest. A small populationof pancreatic cancer stem cells (CSCs) has been foundto be resistant to chemotherapy and radiation therapy.CSCs are believed to be responsible for tumor initiation,progression and metastasis. The CSC research has recentlyachieved much progress in a variety of solid tumors,including pancreatic cancer to some extent. This leads tofocus on understanding the role of pancreatic CSCs. Thefocus on CSCs may offer new targets for prevention andtreatment of this deadly cancer. We review the most salientdevelopments in important areas of pancreatic CSCs. Here,we provide a review of current updates and new insightson the role of CSCs in pancreatic tumor progression withspecial emphasis on DclK1 and Lgr5, signaling pathwaysaltered by CSCs, and the role of CSCs in prevention andtreatment of PC.

  9. Protein Ubiquitylation in Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Thomas Bonacci

    2010-01-01

    Full Text Available Pancreatic cancer is one of the worst, as almost 100% of patients will die within 5 years after diagnosis. The tumors are characterized by an early, invasive, and metastatic phenotype, and extreme resistance to all known anticancer therapies. Therefore, there is an urgent need to develop new investigative strategies in order to identify new molecular targets and, possibly, new drugs to fight this disease efficiently. Whereas it has been known for more than 3 decades now, ubiquitylation is a post-translational modification of protein that only recently emerged as a major regulator of many biological functions, dependent and independent on the proteasome, whose failure is involved in many human diseases, including cancer. Indeed, despite its role in promoting protein degradation through the proteasome, ubiquitylation is now known to regulate diverse cellular processes, such as membrane protein endocytosis and intracellular trafficking, assembly of protein complexes, gene transcription, and activation or inactivation of enzymes. Taking into account that ubiquitylation machinery is a three-step process involving hundreds of proteins, which is countered by numerous ubiquitin hydrolases, and that the function of ubiquitylation relies on the recognition of the ubiquitin signals by hundreds of proteins containing a ubiquitin binding domain (including the proteasome, the number of possible therapeutic targets is exceptionally vast and will need to be explored carefully for each disease. In the case of pancreatic cancer, the study and the identification of specific alteration(s in protein ubiquitylation may help to explain its severity and may furnish more specific targets for more efficient therapies.

  10. Pancreatic cancer-Pathology%胰腺癌:病理学

    Institute of Scientific and Technical Information of China (English)

    Frank Bergmann; Irene Esposito; Esther Herpel; Peter Schirmacher

    2007-01-01

    @@ Introductions Pancreatic ductal adenocarcinoma (frequently simply being referred to as "pancreatic cancer") represents the most frequent neoplasm of the pancreas, accounting for 85% to 90% of all pancreatic tumors [1, 2].

  11. State of the art biological therapies in pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    2016-01-01

    Pancreatic ductal adenocarcinoma (PDAC) is one ofthe most lethal malignancies with a five-year survivalrate of approximately 5%. Several target agents havebeen tested in PDAC, but almost all have failed todemonstrate efficacy in late phase clinical trials, despitethe better understanding of PDAC molecular biologygenerated by large cancer sequencing initiatives in thepast decade. Eroltinib (a small-molecule tyrosine-kinaseinhibitor of epidermal growth factor receptor) plusgemcitabine is the only schedule with a biological agentapproved for advanced pancreatic cancer, but it hasresulted in a very modest survival benefit in unselectedpatients. In our work, we report a summary of the mainclinical trials (closed and ongoing) that refer to biologicaltherapy evaluation in pancreatic cancer treatment.

  12. 微小RNA在胰腺癌中的研究进展%Research Advancement of MicroRNA on Pancreatic Cancer

    Institute of Scientific and Technical Information of China (English)

    姚汝铖; 郑军; 邢荣春

    2012-01-01

    Objective To summarize the domestic and abroad articles related to the research on the relation between microRNA (miRNA) and pancreatic cancer, and explore the important effects of miRNA expression patterns in diagnosis of pancreatic cancer. Methods "microRNA and pancreatic cancer" were searched as key words by PubMed and CNKI series full-text database retrieval systems from 2000 to 2012. Totally 60 English papers and 15 Chinese papers were obtained. Choice criteria: the basic research of miRNA and pancreatic cancer, the clinical research of miRNA and pancreatic cancer, and the prospect of miRNA in pancreatic cancer diagnosis and treatment. According to the choice criteria, 31 papers were finally analyzed. Results The miRNA expression spectrum and specific miRNA expression such as miR-21, miR-34, miR-217, miR-196a, miR-l0a, miR-155, miR-221, miR-222, miR-181a, miR-181b, miR-181d, and the family members of miR-200 and let-7 might be used as rumor markers to differentiate pancreatic cancer from normal pancreas, chronic pancreatitis or pancreatic endocrine tumors, and might be used as prognostic factor to predict the outcome. Conclusions miRNA expression spectrum are not only related to diagnosis of pancreatic cancer, but also have provided a new research direction and method for gene therapy of pancreatic cancer.%目的 总结微小RNA (microRNA,miRNA)与胰腺癌之间关系的研究现状,探讨其表达谱在胰腺癌诊断中的重要作用.方法 应用PubMed及CNKI期刊全文数据库检索系统,以“microRNA、胰腺癌”等为关键词,检索2000~2012年的相关文献,共检索到英文文献60篇和中文文献15篇.纳入标准为:miRNA与胰腺癌的基础与临床研究以及miRNA在胰腺癌诊治中的前景.根据纳入标准,纳入31篇文献.结果 研究发现,miRNA表达谱如miR-21、miR-34、miR-217、miR-196a、miR- 10a、miR-155、miR-221、miR-222、miR-181a、miR-181b、miR-181d、miR-200、let-7等家族成员可作为肿瘤标志物

  13. Management of borderline resectable pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    Amit; Mahipal; Jessica; Frakes; Sarah; Hoffe; Richard; Kim

    2015-01-01

    Pancreatic cancer is the fourth most common cause of cancer death in the United States. Surgery remains the only curative option; however only 20% of the patients have resectable disease at the time of initialpresentation. The definition of borderline resectable pancreatic cancer is not uniform but generally denotes to regional vessel involvement that makes it unlikely to have negative surgical margins. The accurate staging of pancreatic cancer requires triple phase computed tomography or magnetic resonance imaging of the pancreas. Management of patients with borderline resectable pancreatic cancer remains unclear. The data for treatment of these patients is primarily derived from retrospective single institution experience. The prospective trials have been plagued by small numbers and poor accrual. Neoadjuvant therapy is recommended and typically consists of chemotherapy and radiation therapy. The chemotherapeutic regimens continue to evolve along with type and dose of radiation therapy. Gemcitabine or 5-fluorouracil based chemotherapeutic combinations are administered. The type and dose of radiation vary among different institutions. With neoadjuvant treatment, approximately 50% of the patients are able to undergo surgical resections with negative margins obtained in greater than 80% of the patients. Newer trials are attempting to standardize the definition of borderline resectable pancreatic cancer and treatment regimens. In this review, we outline the definition, imaging requirements and management of patients with borderline resectable pancreatic cancer.

  14. Molecular aspects of carcinogenesis in pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    Alexandros Koliopanos; Constantinos Avgerinos; Constantina Paraskeva; Zisis Touloumis; Dionisisa Kelgiorgi; Christos Dervenis

    2008-01-01

    BACKGROUND: Pancreatic cancer (PCa) is one of the most aggressive human solid tumors, with rapid growth and metastatic spread as well as resistance to chemotherapeutic drugs, leading rapidly to virtually incurable disease. Over the last 20 years, however, signiifcant advances have been made in our understanding of the molecular biology of PCa, with a focus on the cytogenetic abnormalities in PCa cell growth and differentiation. DATA SOURCES: A MEDLINE search and manual cross-referencing were utilized to identify published data for PCa molecular biology studies between 1986 and 2008, with emphasis on genetic alterations and developmental oncology. RESULTS: Activation of oncogenes, deregulation of tumor suppressor and genome maintenance genes, upregulation of growth factors/growth factor receptor signaling cascade systems, and alterations in cytokine expression, have been reported to play important roles in the process of pancreatic carcinogenesis. Alterations in the K-ras proto-oncogene and the p16INK4a, p53, FHIT, and DPC4 tumor suppressor genes occur in a high percentage of tumors. Furthermore, a variety of growth factors are expressed at increased levels. In addition, PCa often exhibits alterations in growth inhibitory pathways and evades apoptosis through p53 mutations and aberrant expression of apoptosis-regulating genes, such as members of the Bcl family. Additional pathways in the development of an aggressive phenotype, local inifltration and metastasis are still under ongoing genetic research. The present paper reviews recent studies on the pathogenesis of PCa, and includes a brief reference to alterations reported for other types of pancreatic tumor. CONCLUSIONS: Advances in molecular genetics and biology have improved our perception of the pathogenesis of PCa. However, further studies are needed to better understand the fundamental changes that occur in PCa, thus leading to better diagnostic and therapeutic management.

  15. Vaccine Therapy in Treating Patients With Colon, Pancreatic, or Lung Cancer

    Science.gov (United States)

    2015-04-27

    Recurrent Colon Cancer; Extensive Stage Small Cell Lung Cancer; Stage III Pancreatic Cancer; Stage III Rectal Cancer; Limited Stage Small Cell Lung Cancer; Recurrent Pancreatic Cancer; Recurrent Rectal Cancer; Stage III Non-small Cell Lung Cancer; Stage I Pancreatic Cancer; Stage II Non-small Cell Lung Cancer; Stage IVB Pancreatic Cancer; Stage II Pancreatic Cancer; Stage III Colon Cancer; Stage IVA Pancreatic Cancer

  16. Optimizing Adjuvant Therapy for Resected Pancreatic Cancer

    Science.gov (United States)

    In this clinical trial, patients with resected pancreatic head cancer will be randomly assigned to receive either gemcitabine with or without erlotinib for 5 treatment cycles. Patients who do not experience disease progression or recurrence will then be r

  17. GEMMs as preclinical models for testing pancreatic cancer therapies

    Directory of Open Access Journals (Sweden)

    Aarthi Gopinathan

    2015-10-01

    Full Text Available Pancreatic ductal adenocarcinoma is the most common form of pancreatic tumour, with a very limited survival rate and currently no available disease-modifying treatments. Despite recent advances in the production of genetically engineered mouse models (GEMMs, the development of new therapies for pancreatic cancer is still hampered by a lack of reliable and predictive preclinical animal models for this disease. Preclinical models are vitally important for assessing therapies in the first stages of the drug development pipeline, prior to their transition to the clinical arena. GEMMs carry mutations in genes that are associated with specific human diseases and they can thus accurately mimic the genetic, phenotypic and physiological aspects of human pathologies. Here, we discuss different GEMMs of human pancreatic cancer, with a focus on the Lox-Stop-Lox (LSL-KrasG12D; LSL-Trp53R172H; Pdx1-cre (KPC model, one of the most widely used preclinical models for this disease. We describe its application in preclinical research, highlighting its advantages and disadvantages, its potential for predicting clinical outcomes in humans and the factors that can affect such outcomes, and, finally, future developments that could advance the discovery of new therapies for pancreatic cancer.

  18. 全身γ刀治疗中晚期胰腺癌的研究进展%Overview of whole body gamma knife for locally advanced pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    刘智惠; 孙大庆

    2012-01-01

    胰腺癌是严重威胁人类健康的疾病之一,但是针对其的有效治疗方法依然非常有限.本文概述了国内全身伽玛刀治疗中晚期胰腺癌的原理和疗效等,简要描述了国外类似的体部立体定向放射治疗(stereotactic body radiation therapy,SBRT)中晚期胰腺癌的情况.总之,国内用全身伽玛刀治疗胰腺癌提高了患者的生存率,不良反应小,对肿瘤进展有较好的控制,这主要是根据伽玛刀的原理提高了病灶区的吸收剂量.尽管国外对与全身伽玛刀作用类似的SBRT治疗的优势仍存在争议,但是他们也逐渐认识到了使用SBRT治疗胰腺癌的一些优点.%Pancreatic cancer is a disease that seriously threatens the health of human beings. The treatment options currently available for pancreatic cancer are still limited. In this article, we describe the principle of whole body gamma knife and SBRT (a treatment similar to whole body gamma knife) for the treatment of advanced pancreatic cancer. By improving the absorbed dose in the lesion, whole body gamma knife can control tumor progression and improve survival in patients with pancreatic cancer with low side effects. Despite that controversy still exists, the advantages of SBRT in the treatment of pancreatic cancer have been gradually recognized in foreign countries.

  19. [Differential diagnosis of pancreatic head cancer].

    Science.gov (United States)

    Kubyshkin, V A; Vishnevskiĭ, V A; Aĭrapetian, A T; Karmazanovskiĭ, G G; Kuntsevich, G I; Starkov, Iu G

    2000-01-01

    The results of clinical, instrumental and laboratory examinations were analyzed for 99 patients. 59 of them had pancreatic head cancer, 40--chronic pseudotumorous pancreatitis. The importance of complex ultrasonic diagnosis in detection of pancreatic diseases (98%), in true diagnosis of unresectable tumors (96.7%), and also in determination of bile ducts lesion level in obstructive jaundice is shown. It was revealed that spiral computed tomography (SCT) had an advantage over computed tomography in diagnosis of pancreatic tumors and in assessment of their resectability. Sensitivity of combined use of US, SCT and tumor marker CA 19-9 in pancreatic cancer diagnosis increases to 95.2%. High diagnostic value of laparoscopy with laparoscopic ultrasonic examination as a method of final assessment of tumor resectability is shown.

  20. Analysis of Dosimetric Parameters Associated With Acute Gastrointestinal Toxicity and Upper Gastrointestinal Bleeding in Locally Advanced Pancreatic Cancer Patients Treated With Gemcitabine-Based Concurrent Chemoradiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Nakamura, Akira [Department of Radiation Oncology and Image-Applied Therapy, Kyoto University Graduate School of Medicine, Kyoto (Japan); Shibuya, Keiko, E-mail: kei@kuhp.kyoto-u.ac.jp [Department of Radiation Oncology and Image-Applied Therapy, Kyoto University Graduate School of Medicine, Kyoto (Japan); Matsuo, Yukinori; Nakamura, Mitsuhiro; Shiinoki, Takehiro; Mizowaki, Takashi; Hiraoka, Masahiro [Department of Radiation Oncology and Image-Applied Therapy, Kyoto University Graduate School of Medicine, Kyoto (Japan)

    2012-10-01

    Purpose: To identify the dosimetric parameters associated with gastrointestinal (GI) toxicity in patients with locally advanced pancreatic cancer (LAPC) treated with gemcitabine-based chemoradiotherapy. Methods and Materials: The data from 40 patients were analyzed retrospectively. Chemoradiotherapy consisted of conventional fractionated three-dimensional radiotherapy and weekly gemcitabine. Treatment-related acute GI toxicity and upper GI bleeding (UGB) were graded according to the Common Toxicity Criteria Adverse Events, version 4.0. The dosimetric parameters (mean dose, maximal absolute dose which covers 2 cm{sup 3} of the organ, and absolute volume receiving 10-50 Gy [V{sub 10-50}]) of the stomach, duodenum, small intestine, and a composite structure of the stomach and duodenum (StoDuo) were obtained. The planning target volume was also obtained. Univariate analyses were performed to identify the predictive factors for the risk of grade 2 or greater acute GI toxicity and grade 3 or greater UGB, respectively. Results: The median follow-up period was 15.7 months (range, 4-37). The actual incidence of acute GI toxicity was 33%. The estimated incidence of UGB at 1 year was 20%. Regarding acute GI toxicity, a V{sub 50} of {>=}16 cm{sup 3} of the stomach was the best predictor, and the actual incidence in patients with V{sub 50} <16 cm{sup 3} of the stomach vs. those with V{sub 50} of {>=}16 cm{sup 3} was 9% vs. 61%, respectively (p = 0.001). Regarding UGB, V{sub 50} of {>=}33 cm{sup 3} of the StoDuo was the best predictor, and the estimated incidence at 1 year in patients with V{sub 50} <33 cm{sup 3} of the StoDuo vs. those with V{sub 50} {>=}33 cm{sup 3} was 0% vs. 44%, respectively (p = 0.002). The dosimetric parameters correlated highly with one another. Conclusion: The irradiated absolute volume of the stomach and duodenum are important for the risk of acute GI toxicity and UGB. These results could be helpful in escalating the radiation doses using novel

  1. Diabetes Type 2 and Pancreatic Cancer: A History Unfolding

    OpenAIRE

    Andre Souza; Khawaja Irfan; Faisal Masud; Muhammad Wasif Saif

    2016-01-01

    Pancreatic Cancer is the fourth cause of cancer-related deaths in the United States. Up to 80% of pancreatic cancer patients present with either new-onset type 2 diabetes or impaired glucose tolerance at the time of diagnosis. Recent literature suggests that diabetes mellitus type 2 is a risk factor, a manifestation and a prognostic factor for pancreatic cancer. This article is intended to clarify the evidence about diabetes as a risk factor for pancreatic cancer.

  2. Diabetes Type 2 and Pancreatic Cancer: A History Unfolding

    Directory of Open Access Journals (Sweden)

    Andre De Souza

    2016-03-01

    Full Text Available Pancreatic Cancer is the fourth cause of cancer-related deaths in the United States. Up to 80% of pancreatic cancer patients present with either new-onset type 2 diabetes or impaired glucose tolerance at the time of diagnosis. Recent literature suggests that diabetes mellitus type 2 is a risk factor, a manifestation and a prognostic factor for pancreatic cancer. This article is intended to clarify the evidence about diabetes as a risk factor for pancreatic cancer.

  3. Treatment of Pancreatic Cancer with Pharmacological Ascorbate.

    Science.gov (United States)

    Cieslak, John A; Cullen, Joseph J

    2015-01-01

    The prognosis for patients diagnosed with pancreatic cancer remains dismal, with less than 3% survival at 5 years. Recent studies have demonstrated that high-dose, intravenous pharmacological ascorbate (ascorbic acid, vitamin C) induces cytotoxicity and oxidative stress selectively in pancreatic cancer cells vs. normal cells, suggesting a promising new role of ascorbate as a therapeutic agent. At physiologic concentrations, ascorbate functions as a reducing agent and antioxidant. However, when pharmacological ascorbate is given intravenously, it is possible to achieve millimolar plasma concentration. At these pharmacological levels, and in the presence of catalytic metal ions, ascorbate can induce oxidative stress through the generation of hydrogen peroxide (H2O2). Recent in vitro and in vivo studies have demonstrated ascorbate oxidation occurs extracellularly, generating H2O2 flux into cells resulting in oxidative stress. Pharmacologic ascorbate also inhibits the growth of pancreatic tumor xenografts and displays synergistic cytotoxic effects when combined with gemcitabine in pancreatic cancer. Phase I trials of pharmacological ascorbate in pancreatic cancer patients have demonstrated safety and potential efficacy. In this chapter, we will review the mechanism of ascorbate-induced cytotoxicity, examine the use of pharmacological ascorbate in treatment and assess the current data supporting its potential as an adjuvant in pancreatic cancer.

  4. In vitro models of pancreatic cancer for translational oncology research

    Science.gov (United States)

    Feldmann, Georg; Rauenzahn, Sherri; Maitra, Anirban

    2009-01-01

    Background Pancreatic cancer is a disease of near uniform fatality and the overwhelming majority of patients succumb to their advanced malignancy within a few months of diagnosis. Despite considerable advances in our understanding of molecular mechanisms underlying pancreatic carcinogenesis, this knowledge has not yet been fully translated into clinically available treatment strategies that yield significant improvements in disease free or overall survival. Objective Cell line-based in vitro model systems provide powerful tools to identify potential molecular targets for therapeutic intervention as well as for initial pre-clinical evaluation of novel drug candidates. Here we provide a brief overview of recent literature on cell line-based model systems of pancreatic cancer and their application in the search for novel therapeutics against this vicious disease. Conclusion While in vitro models of pancreatic cancer are of tremendous value for genetic studies and initial functional screenings in drug discovery, they carry several imanent drawbacks and are often poor in predicting therapeutic response in humans. Therefore, in most instances they are successfully exploited to generate hypothesis and identify molecular targets for novel therapeutics, which are subsequently subject to further in-depth characterization using more advanced in vivo model systems and clinical trials. PMID:20160967

  5. Metformin induces apoptosis of pancreatic cancer cells

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    AIM: To assess the role and mechanism of mefformin in inducing apoptosis of pancreatic cancer cells. METHODS: The human pancreatic cancer cell lines ASPC-1, BxPc-3, PANC-1 and SW1990 were exposed to mefformin. The inhibition of cell proliferation and colony formation via apoptosis induction and S phase arrest in pancreatic cancer cell lines of mefformin was tested.RESULTS: In each pancreatic cancer cell line tested, metformin inhibited cell proliferation in a dose dependent manner in MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium assays). Flow cytometric analysis showed that metformin reduced the number of cells in G1 and increased the percentage of cells in S phase as well as the apoptotic fraction. Enzymelinked immunosorbent assay (EUSA) showed that metformin induced apaptosis in all pancreatic cancer cell lines. In Western blot studies, metformin induced oly-ADP-ribose polymerase(PARP) cleavage (an indicator of aspase activation) in all pancreatic cancer cell lines. The general caspase inhibitor (VAD-fmk) completely abolished metformin-induced PARP cleavage and apoptosis in ASPC-1 BxPc-3 and PANC-1, the caspase-8 specific inhibitor (IETD-fmk) and the caspase-9 specific inhibitor (LEHD-fmk) only partially abrogated metformin-induced apoptosis and PARP cleavage in BxPc-3 and PANC-1 cells. We also observed that metformin treatment ramatically reduced epidermal growth factor receptor (EGFR) and phosphorylated mitogen activated protein kinase (P-MAPK) in both a time- and dose-dependent manner in all cell lines tested.CONCLUSION: Metformin significantly inhibits cell proliferation and apoptosis in all pancreatic cell lines. And the metformin-induced apoptosis is associated with PARP leavage, activation of caspase-3, -8, and -9 in a time- and dose-dependent manner. Hence, both caspase-8 and -9-initiated apoptotic signaling pathways contribute to metforrnin-induced apoptosis in pancreatic cell lines.

  6. Evaluation and treatment of stage IVb pancreatic cancer

    Energy Technology Data Exchange (ETDEWEB)

    Miyamoto, Hidenori; Kurita, Nobuhiro; Miyake, Hidenori [Tokushima Univ. (Japan). School of Medicine] [and others

    2003-04-01

    Pancreatic cancer is often detected in a far advanced stage and the prognosis is still extremely poor. A clinicopathological study was made on 49 patients with Stage IVb pancreatic cancer treated at our department from March 1994 to February 2002. In this study, patient factors (age and gender), tumor factors (hepatic metastasis, peritoneal dissemination, and distant metastasis), and treatment factors (systemic chemotherapy, intra- and post-operative radiotherapy, some treatments to hepatic metastasis, and surgical resection) were examined, and the survival was evaluated statistically. Overall mean survival was 150 days and the 1-year survival rate was 0%. With multivariate analysis, prognostic factors were hepatic metastasis, peritoneal dissemination and some treatments to hepatic metastasis. In advanced pancreatic cancer with hepatic metastasis, the prognostic factor was just some treatments to hepatic metastasis. Systemic chemotherapy with somatostatin analog was ineffective. At present we use either gemcitabine or 5FU in systemic chemotherapy for Stage IVb pancreatic cancers without hepatic metastasis, and conduct hepatic arterial infusion therapy for those with hepatic metastasis. (author)

  7. Mediterranean diet and risk of pancreatic cancer in the European Prospective Investigation into Cancer and Nutrition cohort

    DEFF Research Database (Denmark)

    Molina-Montes, Esther; Sánchez, Maria-Jose; Buckland, Genevieve

    2017-01-01

    BACKGROUND: The Mediterranean diet (MD) has been proposed as a means for cancer prevention, but little evidence has been accrued regarding its potential to prevent pancreatic cancer. We investigated the association between the adherence to the MD and pancreatic cancer risk within the European Pro...... or other definitions of the MD pattern. CONCLUSIONS: A high adherence to the MD is not associated with pancreatic cancer risk in the EPIC study.British Journal of Cancer advance online publication 7 February 2017; doi:10.1038/bjc.2017.14 www.bjcancer.com....

  8. Intensity modulated radiotherapy as neoadjuvant chemoradiation for the treatment of patients with locally advanced pancreatic cancer. Outcome analysis and comparison with a 3D-treated patient cohort

    Energy Technology Data Exchange (ETDEWEB)

    Combs, S.E.; Habermehl, D.; Kessel, K.; Brecht, I. [Univ. Hospital of Heidelberg (Germany). Dept. of Radiation Oncology; Bergmann, F.; Schirmacher, P. [Univ. Hospital of Heidelberg (Germany). Dept. of Pathology; Werner, J.; Buechler, M.W. [Univ. Hospital of Heidelberg (Germany). Dept. of Surgery; Jaeger, D. [National Center for Tumor Diseases (NCT), Heidelberg (Germany); Debus, J. [Univ. Hospital of Heidelberg (Germany). Dept. of Radiation Oncology; Deutsches Krebsforschungszentrum (DKFZ), Heidelberg (Germany). Clinical Cooperation Unit Radiation Oncology

    2013-09-15

    Background: To evaluate outcome after intensity modulated radiotherapy (IMRT) compared to 3D conformal radiotherapy (3D-RT) as neoadjuvant treatment in patients with locally advanced pancreatic cancer (LAPC). Materials and methods: In total, 57 patients with LAPC were treated with IMRT and chemotherapy. A median total dose of 45 Gy to the PTV {sub baseplan} and 54 Gy to the PTV {sub boost} in single doses of 1.8 Gy for the PTV {sub baseplan} and median single doses of 2.2 Gy in the PTV {sub boost} were applied. Outcomes were evaluated and compared to a large cohort of patients treated with 3D-RT. Results: Overall treatment was well tolerated in all patients and IMRT could be completed without interruptions. Median overall survival was 11 months (range 5-37.5 months). Actuarial overall survival at 12 and 24 months was 36 % and 8 %, respectively. A significant impact on overall survival could only be observed for a decrease in CA 19-9 during treatment, patients with less pre-treatment CA 19-9 than the median, as well as weight loss during treatment. Local progression-free survival was 79 % after 6 months, 39 % after 12 months, and 13 % after 24 months. No factors significantly influencing local progression-free survival could be identified. There was no difference in overall and progression-free survival between 3D-RT and IMRT. Secondary resectability was similar in both groups (26 % vs. 28 %). Toxicity was comparable and consisted mainly of hematological toxicity due to chemotherapy. Conclusion: IMRT leads to a comparable outcome compared to 3D-RT in patients with LAPC. In the future, the improved dose distribution, as well as advances in image-guided radiotherapy (IGRT) techniques, may improve the use of IMRT in local dose escalation strategies to potentially improve outcome. (orig.)

  9. Preclinical fluorescent mouse models of pancreatic cancer

    Science.gov (United States)

    Bouvet, Michael; Hoffman, Robert M.

    2007-02-01

    Here we describe our cumulative experience with the development and preclinical application of several highly fluorescent, clinically-relevant, metastatic orthotopic mouse models of pancreatic cancer. These models utilize the human pancreatic cancer cell lines which have been genetically engineered to selectively express high levels of the bioluminescent green fluorescent (GFP) or red fluorescent protein (RFP). Fluorescent tumors are established subcutaneously in nude mice, and tumor fragments are then surgically transplanted onto the pancreas. Locoregional tumor growth and distant metastasis of these orthotopic implants occurs spontaneously and rapidly throughout the abdomen in a manner consistent with clinical human disease. Highly specific, high-resolution, real-time visualization of tumor growth and metastasis may be achieved in vivo without the need for contrast agents, invasive techniques, or expensive imaging equipment. We have shown a high correlation between florescent optical imaging and magnetic resonance imaging in these models. Alternatively, transplantation of RFP-expressing tumor fragments onto the pancreas of GFP-expressing transgenic mice may be used to facilitate visualization of tumor-host interaction between the pancreatic tumor fragments and host-derived stroma and vasculature. Such in vivo models have enabled us to serially visualize and acquire images of the progression of pancreatic cancer in the live animal, and to demonstrate the real-time antitumor and antimetastatic effects of several novel therapeutic strategies on pancreatic malignancy. These fluorescent models are therefore powerful and reliable tools with which to investigate human pancreatic cancer and therapeutic strategies directed against it.

  10. Mitochondrial uncoupling protein 2 and pancreatic cancer: a new potential target therapy.

    Science.gov (United States)

    Donadelli, Massimo; Dando, Ilaria; Dalla Pozza, Elisa; Palmieri, Marta

    2015-03-21

    Overall 5-years survival of pancreatic cancer patients is nearly 5%, making this cancer type one of the most lethal neoplasia. Furthermore, the incidence rate of pancreatic cancer has a growing trend that determines a constant increase in the number of deceases caused by this pathology. The poor prognosis of pancreatic cancer is mainly caused by delayed diagnosis, early metastasis of tumor, and resistance to almost all tested cytotoxic drugs. In this respect, the identification of novel potential targets for new and efficient therapies should be strongly encouraged in order to improve the clinical management of pancreatic cancer. Some studies have shown that the mitochondrial uncoupling protein 2 (UCP2) is over-expressed in pancreatic cancer as compared to adjacent normal tissues. In addition, recent discoveries established a key role of UCP2 in protecting cancer cells from an excessive production of mitochondrial superoxide ions and in the promotion of cancer cell metabolic reprogramming, including aerobic glycolysis stimulation, promotion of cancer progression. These observations together with the demonstration that UCP2 repression can synergize with standard chemotherapy to inhibit pancreatic cancer cell growth provide the molecular rationale to consider UCP2 as a potential therapeutic target for pancreatic cancer. In this editorial, recent advances describing the relationship between cancer development and mitochondrial UCP2 activity are critically provided.

  11. Intraoperative radiofrequency ablation combined with ~(125)iodine seed implantation for unresectable pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    AIM: To evaluate the feasibility, efficacy and safety of intraoperative radiofrequency ablation (RFA) combined with 125 iodine seed implantation for unresectable pancreatic cancer. METHODS: Thirty-two patients (21 males and 11 females) at the age of 68 years (range 48-90 years) with unresectable locally advanced pancreatic cancer admitted to our hospital from January 2006 to May 2008 were enrolled in this study. The tumor, 4-12 cm in diameter, located in pancreatic head of 23 patients and in pancreatic body...

  12. Microbiota, oral microbiome, and pancreatic cancer.

    Science.gov (United States)

    Michaud, Dominique S; Izard, Jacques

    2014-01-01

    Only 30% of patients with a diagnosis of pancreatic cancer survive 1 year after the diagnosis. Progress in understanding the causes of pancreatic cancer has been made, including solidifying the associations with obesity and diabetes, and a proportion of cases should be preventable through lifestyle modifications. Unfortunately, identifying reliable biomarkers of early pancreatic cancer has been extremely challenging, and no effective screening modality is currently available for this devastating form of cancer. Recent data suggest that the microbiota may play a role in the disease process, but many questions remain. Future studies focusing on the human microbiome, both etiologically and as a marker of disease susceptibility, should shed light on how to better tackle prevention, early detection, and treatment of this highly fatal disease.

  13. Increase in Annual Number of Pancreatic Head Resections Does not Affect Mortality of Pancreatic Cancer in the United Kingdom

    Directory of Open Access Journals (Sweden)

    Efthymios Ypsilantis

    2009-07-01

    Full Text Available Dear Sir, Lee and Saif urged for new effective methods for early diagnosis of pancreatic head adenocarcinoma, emphasizing that at the time of initial presentation, the majority of patients have non-resectable tumours [1]. Also, Li and Saif, in their thorough overview of current advancements in the management of the disease, summarized that pancreatic cancer requires a multidisciplinary therapeutic approach that should aim to increase the chances of surgical resection [2].

  14. Multimodality Treatment in Pancreatic and Periampullary Cancer

    NARCIS (Netherlands)

    M.J.M. Morak (Marjolein)

    2015-01-01

    markdownabstract__Abstract__ Pancreatic cancer is the eight most common form of cancer in Europe with 96.000 new cases yearly. This incidence closely matches the mortality rate, thus revealing the aggressive behaviour of this tumour. Five-year survival after diagnosis is only 5% with a median overa

  15. Phase-II study on stereotactic radiotherapy of locally advanced pancreatic carcinoma

    DEFF Research Database (Denmark)

    Høyer, Morten; Roed, Henrik; Sengeløv, Lisa;

    2005-01-01

    BACKGROUND AND PURPOSE: The majority of patients with pancreatic cancer have advanced disease at the time of diagnosis and are not amenable for surgery. Stereotactic radiotherapy (SRT) may be an alternative treatment for patients with locally advanced disease. The effect of SRT was investigated...

  16. Vitamin D for the prevention and treatment of pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    Kun-Chun Chiang; Tai C Chen

    2009-01-01

    Pancreatic cancer is ranked fifth among cancer-related deaths worldwide with a 5-year survival rate of less than 5%. Currently, surgery is the only effective therapy. However, most patients are diagnosed in the late stage and are not suitable for receiving curative surgery. Moreover, pancreatic cancer doesn't respond well to traditional chemotherapy and radiotherapy,leaving little effective treatment for advanced pancreatic cancer cases. 1α,25-dihydroxyvitamin D3 [1α,25(OH)2D3], the biologically active form of vitamin D3, was originally identified during studies of calcium and bone metabolism, though it is now recognized that it exerts biological effects in almost every tissue in the body. Abundant evidence has shown that 1α,25(OH)2D3 has antiproliferative, apoptotic, pro-differentiation and antiangiogensis effects in many types of cancer cells invivoand in vitro, including breast, prostate, and colon.Similarly, the antitumor growth effect of 1α,25(OH)2D3 on pancreatic cells has been demonstrated. The clinical use of 1α,25(OH)2D3 is impeded by the lethal side effects of hypercalcemia and hypercalciuria. Therefore,1α,25(OH)2D3 analogs, which are either equipotent or more potent than 1α,25(OH)2D3 in inhibiting tumor cell growth but with fewer hypercalcemic and hypercalciuric side effects, have been developed for the treatment of different cancers. Recently, a preclinical study demonstrated that a less calcemic analog of 1α,25(OH)2D3, 19-nor-1α,25(OH)2D2 (Paricalcitol),is effective in inhibiting tumor growth invitroand invivo, viaupregulation of p21 and p27 tumor suppressor genes. Studies on the anti-tumor effects of a more potent analog of Paricalcitol are underway.1α,25(OH)2D3 and its analogs are potentially attractive novel therapies for pancreatic cancer.(c) 2009 The WJG Press and Baishideng. All rights reserved.

  17. Multimodality treatment of recurrent pancreatic cancer: Mith or reality?

    Institute of Scientific and Technical Information of China (English)

    Cosimo; Sperti; Lucia; Moletta; Stefano; Merigliano

    2015-01-01

    Pancreatic adenocarcinoma is the fourth cause of cancerrelated death in the United States. Surgery is the only potentially curative treatment, but most patients present at diagnosis with unresectable or metastatic disease. Moreover, even with an R0 resection, the majority of patients will die of disease recurrence. Most recurrencesoccur in the first 2-year after pancreatic resection, and are commonly located in the abdomen, even if distant metastases can occur. Recurrent pancreatic adenocarcinoma remains a significant therapeutic challenge, due to the limited role of surgery and radiochemotherapy. Surgical management of recurrence is usually unreliable because tumor relapse typically presents as a technically unresectable, or as multifocal disease with an aggressive growth. Therefore, treatment of patients with recurrent pancreatic adenocarcinoma has historically been limited to palliative chemotherapy or supportive care. Only few data are available in the Literature about this issue, even if in recent years more studies have been published to determine whether treatment after recurrence have any effect on patients outcome. Recent therapeutic advances have demonstrated the potential to improve survival in selected patients who had undergone resection for pancreatic cancer. Multimodality management of recurrent pancreatic carcinoma may lead to better survival and quality of life in a small but significant percentage of patients; however, more and larger studies are needed to clarify the role of the different therapeutic options and the optimal way to combine them.

  18. Assessment value of quantitative indexes of pancreatic CT perfusion scanning for malignant degree of pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    Jiang-Xia Lei

    2016-01-01

    Objective:To analyze the assessment value of the quantitative indexes of pancreatic CT perfusion scanning for malignant degree of pancreatic cancer.Methods:A total of 58 patients with space-occupying pancreatic lesions were divided into 20 patients with pancreatic cancer and 38 patients with benign pancreatic lesions after pancreatic CT perfusion. Patients with pancreatic cancer received palliative surgery, and the cancer tissue and para-carcinoma tissue specimens were collected during operation. The differences in pancreatic CT perfusion scanning parameter values and serum tumor marker levels were compared between patients with pancreatic cancer and patients with benign pancreatic lesions, mRNA expression levels of malignant molecules in pancreatic cancer tissue and para-carcinoma tissue were further determined, and the correlation between pancreatic CT perfusion scanning parameter values and malignant degree of pancreatic cancer was analyzed.Results:CT perfusion scanning BF, BV and Per values of patients with pancreatic cancer were lower than those of patients with benign pancreatic lesions; serum CA19-9, CEA, CA125 and CA242 levels were higher than those of patients with benign pancreatic lesions (P<0.05); mRNA expression levels of Bcl-2, Bcl-xL andsurvivin in pancreatic cancer tissue samples were higher than those in para-carcinoma tissue samples, and mRNA expression levels ofP53 andBax were lower than those in para-carcinoma tissue samples (P<0.05); CT perfusion scanning parameters BF, BV and Per values of patients with pancreatic cancer were negatively correlated with CA19-9, CEA, CA125 and CA242 levels in serum as well as mRNA expression levels ofBcl-2, Bcl-xL and survivinin pancreatic cancer tissue, and positively correlated with mRNA expression levels ofP53andBaxin pancreatic cancer tissue (P<0.05).Conclusions:Pancreatic CT perfusion scanning is a reliable way to judge the malignant degree of pancreatic cancer and plays a positive role in guiding clinical

  19. Current Surgical Aspects of Palliative Treatment for Unresectable Pancreatic Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Karapanos, Konstantinos, E-mail: dr.kostaskarapanos@gmail.com; Nomikos, Iakovos N. [Department of Surgery (B' Unit), METAXA Cancer Memorial Hospital, Piraeus (Greece)

    2011-02-11

    Despite all improvements in both surgical and other conservative therapies, pancreatic cancer is steadily associated with a poor overall prognosis and remains a major cause of cancer mortality. Radical surgical resection has been established as the best chance these patients have for long-term survival. However, in most cases the disease has reached an incurable state at the time of diagnosis, mainly due to the silent clinical course at its early stages. The role of palliative surgery in locally advanced pancreatic cancer mainly involves patients who are found unresectable during open surgical exploration and consists of combined biliary and duodenal bypass procedures. Chemical splanchnicectomy is another modality that should also be applied intraoperatively with good results. There are no randomized controlled trials evaluating the outcomes of palliative pancreatic resection. Nevertheless, data from retrospective reports suggest that this practice, compared with bypass procedures, may lead to improved survival without increasing perioperative morbidity and mortality. All efforts at developing a more effective treatment for unresectable pancreatic cancer have been directed towards neoadjuvant and targeted therapies. The scenario of downstaging tumors in anticipation of a future oncological surgical resection has been advocated by trials combining gemcitabine with radiation therapy or with the tyrosine kinase inhibitor erlotinib, with promising early results.

  20. Transversal Descriptive Study of Xenobiotic Exposures in Patients with Chronic Pancreatitis and Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Cara Yvonne Jeppe

    2008-03-01

    Full Text Available There have been a substantial number of reports in the literature linking pancreatitis and pancreatic cancer to certain xenobiotics and occupations. It has been hypothesized that exposure to volatile hydrocarbons and particularly petrochemicals increases susceptibility to pancreatitis. We performed a study aimed to enumerate occupational and environmental xenobiotics described in the literature as potential risk factors for pancreatitis and to document exposures to these in chronic pancreatitis patients presenting with chronic pain for surgery.

  1. Phase 2 Trial of Induction Gemcitabine, Oxaliplatin, and Cetuximab Followed by Selective Capecitabine-Based Chemoradiation in Patients With Borderline Resectable or Unresectable Locally Advanced Pancreatic Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Esnaola, Nestor F. [Department of Surgery, Hollings Cancer Center, Medical University of South Carolina, Charleston, South Carolina (United States); Chaudhary, Uzair B.; O' Brien, Paul [Division of Hematology and Oncology, Department of Internal Medicine, Hollings Cancer Center, Medical University of South Carolina, Charleston, South Carolina (United States); Garrett-Mayer, Elizabeth [Division of Biostatistics and Epidemiology, Department of Internal Medicine, Hollings Cancer Center, Medical University of South Carolina, Charleston, South Carolina (United States); Camp, E. Ramsay [Department of Surgery, Hollings Cancer Center, Medical University of South Carolina, Charleston, South Carolina (United States); Thomas, Melanie B. [Division of Hematology and Oncology, Department of Internal Medicine, Hollings Cancer Center, Medical University of South Carolina, Charleston, South Carolina (United States); Cole, David J. [Department of Surgery, Hollings Cancer Center, Medical University of South Carolina, Charleston, South Carolina (United States); Montero, Alberto J. [Division of Hematology and Oncology, Department of Internal Medicine, Hollings Cancer Center, Medical University of South Carolina, Charleston, South Carolina (United States); Hoffman, Brenda J.; Romagnuolo, Joseph [Division of Gastroenterology and Hepatology, Department of Internal Medicine, Hollings Cancer Center, Medical University of South Carolina, Charleston, South Carolina (United States); Orwat, Kelly P. [Department of Radiation Oncology, Hollings Cancer Center, Medical University of South Carolina, Charleston, South Carolina (United States); Marshall, David T., E-mail: marshadt@musc.edu [Department of Radiation Oncology, Hollings Cancer Center, Medical University of South Carolina, Charleston, South Carolina (United States)

    2014-03-15

    Purpose: To evaluate, in a phase 2 study, the safety and efficacy of induction gemcitabine, oxaliplatin, and cetuximab followed by selective capecitabine-based chemoradiation in patients with borderline resectable or unresectable locally advanced pancreatic cancer (BRPC or LAPC, respectively). Methods and Materials: Patients received gemcitabine and oxaliplatin chemotherapy repeated every 14 days for 6 cycles, combined with weekly cetuximab. Patients were then restaged; “downstaged” patients with resectable disease underwent attempted resection. Remaining patients were treated with chemoradiation consisting of intensity modulated radiation therapy (54 Gy) and concurrent capecitabine; patients with borderline resectable disease or better at restaging underwent attempted resection. Results: A total of 39 patients were enrolled, of whom 37 were evaluable. Protocol treatment was generally well tolerated. Median follow-up for all patients was 11.9 months. Overall, 29.7% of patients underwent R0 surgical resection (69.2% of patients with BRPC; 8.3% of patients with LAPC). Overall 6-month progression-free survival (PFS) was 62%, and median PFS was 10.4 months. Median overall survival (OS) was 11.8 months. In patients with LAPC, median OS was 9.3 months; in patients with BRPC, median OS was 24.1 months. In the group of patients who underwent R0 resection (all of which were R0 resections), median survival had not yet been reached at the time of analysis. Conclusions: This regimen was well tolerated in patients with BRPC or LAPC, and almost one-third of patients underwent R0 resection. Although OS for the entire cohort was comparable to that in historical controls, PFS and OS in patients with BRPC and/or who underwent R0 resection was markedly improved.

  2. Clinical Usefulness of {sup 18}F-Fluorodeoxyglucose-Positron Emission Tomography in Patients With Locally Advanced Pancreatic Cancer Planned to Undergo Concurrent Chemoradiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Jee Suk; Choi, Seo Hee; Lee, Youngin; Kim, Kyung Hwan [Department of Radiation Oncology, Yonsei University College of Medicine, Seoul (Korea, Republic of); Park, Jeong Youp; Song, Si Young [Department of Internal Medicine, Yonsei University College of Medicine, Seoul (Korea, Republic of); Cho, Arthur; Yun, Mijin; Lee, Jong Doo [Department of Nuclear Medicine, Yonsei University College of Medicine, Seoul (Korea, Republic of); Seong, Jinsil, E-mail: jsseong@yuhs.ac [Department of Radiation Oncology, Yonsei University College of Medicine, Seoul (Korea, Republic of)

    2014-09-01

    Purpose: To assess the role of coregistered {sup 18}F-fluorodeoxyglucose positron emission tomography (FDG-PET) in detecting radiographically occult distant metastasis (DM) at staging in patients with locally advanced pancreatic cancer (LAPC) and to study whether FDG-PET parameters can predict relatively long-term survival in patients who are more likely to benefit from chemoradiation therapy (CRT). Methods and Materials: From our institutional database, we identified 388 LAPC patients with M0 on conventional computed tomography (CT) who were planned to undergo CRT. Coregistered FDG-PET staging was offered to all patients, and follow-up FDG-PET was used at the clinical discretion of the physician. Results: FDG-PET detected unsuspected CT-occult DM in 33% of all 388 patients and allowed them to receive systemic therapy immediately. The remaining 260 patients (PET-M0) underwent CRT selectively as an initial treatment. Early DM arose in 13.1% of 260 patients, and the 1-year estimated locoregional recurrence rate was 5.4%. Median overall survival (OS) and progression-free survival (PFS) were 14.6 and 9.3 months, respectively, at a median follow-up time of 32.3 months (range, 10-99.1 months). Patients with a baseline standardized uptake value (SUV) <3.5 and/or SUV decline ≥60% had significantly better OS and PFS than those having none, even after adjustment for all potential confounding variables (all P<.001). Conclusions: FDG-PET can detect radiographically occult DM at staging in one-third of patients and spare them from the potentially toxic therapy. Additionally, FDG-PET parameters including baseline SUV and SUV changes may serve as useful clinical markers for predicting the prognosis in LAPC patients.

  3. Gemcitabine/cisplatin versus 5-fluorouracil/mitomycin C chemoradiotherapy in locally advanced pancreatic cancer: a retrospective analysis of 93 patients

    Directory of Open Access Journals (Sweden)

    Sauer Rolf

    2011-07-01

    Full Text Available Abstract Background Despite of a growing number of gemcitabine based chemoradiotherapy studies in locally advanced pancreatic cancer (LAPC, 5-fluorouracil based regimens are still regarded to be standard and the debate of superiority between the two drugs is going on. The aim of this retrospective analysis was to evaluate the effect of two concurrent chemoradiotherapy regimens using 5-fluorouracil or gemcitabine to compare their effect and tolerance. Methods We have performed a single centre retrospective analysis of 93 patients treated with conventionally fractionated radiotherapy of 55.8 Gray using either concurrent 5-fluorouracil, 1 g/m² on days 1-5 and 29-33 of radiotherapy and 10 mg/m² of mitomycin C on day 1, 29 of radiotherapy (FM group, 35 patients versus gemcitabine (300 mg/m² and cisplatin, (30 mg/m² on days 1, 8, 22, and 29 (GC group, 58 patients. Primary endpoint was the median overall survival (OS rate. Results The median OS rate was 12.7 months in the GC group and 9.7 months in the FM group. The 1-year OS rate was 53% versus 40%, respectively (p = 0.009. GC led to more grade 3 leukocytopenia and thrombocytopenia than FM, but not to more grade 4 myelosuppression. Thrombocytopenia was the most frequently observed grade 4 toxicity in both groups (11% after FM versus 12% after GC. No grade 3/4 febrile neutropenia was observed. Grade 3 nausea was more common in the FM group (20% versus 9% and grade 4 nausea was observed in one patient per group only. Conclusions GC was superior to FM for overall survival and both regimens were similar in terms of tolerance. We conclude that GC leads to encouraging results and that the use of FM for chemoradiotherapy in LAPC cannot be recommended without concerns.

  4. Imaging and Therapy of Pancreatic Cancer with Phosphatidylserine-Targeted Nanovesicles1

    Science.gov (United States)

    Blanco, Victor M.; Latif, Tahir; Chu, Zhengtao; Qi, Xiaoyang

    2015-01-01

    Pancreatic cancer remains one of the most intractable cancers, with a dismal prognosis reflected by a 5-year survival of ~ 6%. Since early disease symptoms are undefined and specific biomarkers are lacking, about 80% of patients present with advanced, inoperable tumors that represent a daunting challenge. Despite many clinical trials, no single chemotherapy agent has been reliably associated with objective response rates above 10% or median survival longer than 5 to 7 months. Although combination chemotherapy regimens have in recent years provided some improvement, overall survival (8-11 months) remains very poor. There is therefore a critical need for novel therapies that can improve outcomes for pancreatic cancer patients. Here, we present a summary of the current therapies used in the management of advanced pancreatic cancer and review novel therapeutic strategies that target tumor biomarkers. We also describe our recent research using phosphatidylserine-targeted saposin C–coupled dioleoylphosphatidylserine nanovesicles for imaging and therapy of pancreatic cancer. PMID:26055177

  5. Familial pancreatic cancer: Concept, management and issues

    Science.gov (United States)

    Matsubayashi, Hiroyuki; Takaori, Kyoichi; Morizane, Chigusa; Maguchi, Hiroyuki; Mizuma, Masamichi; Takahashi, Hideaki; Wada, Keita; Hosoi, Hiroko; Yachida, Shinichi; Suzuki, Masami; Usui, Risa; Furukawa, Toru; Furuse, Junji; Sato, Takamitsu; Ueno, Makoto; Kiyozumi, Yoshimi; Hijioka, Susumu; Mizuno, Nobumasa; Terashima, Takeshi; Mizumoto, Masaki; Kodama, Yuzo; Torishima, Masako; Kawaguchi, Takahisa; Ashida, Reiko; Kitano, Masayuki; Hanada, Keiji; Furukawa, Masayuki; Kawabe, Ken; Majima, Yoshiyuki; Shimosegawa, Toru

    2017-01-01

    Familial pancreatic cancer (FPC) is broadly defined as two first-degree-relatives with pancreatic cancer (PC) and accounts for 4%-10% of PC. Several genetic syndromes, including Peutz-Jeghers syndrome, hereditary pancreatitis, hereditary breast-ovarian cancer syndrome (HBOC), Lynch syndrome, and familial adenomatous polyposis (FAP), also have increased risks of PC, but the narrowest definition of FPC excludes these known syndromes. When compared with other familial tumors, proven genetic alterations are limited to a small proportion ( Caucasian) and a younger onset are common also in FPC. In European countries, “anticipation” is reported in FPC families, as with other hereditary syndromes; a trend toward younger age and worse prognosis is recognized in the late years. The resected pancreases of FPC kindred often show multiple pancreatic intraepithelial neoplasia (PanIN) foci, with various K-ras mutations, similar to colorectal polyposis seen in the FAP patients. As with HBOC patients, a patient who is a BRCA mutation carrier with unresectable pancreatic cancer (accounting for 0%-19% of FPC patients) demonstrated better outcome following platinum and Poly (ADP-ribose) polymerase inhibitor treatment. Western countries have established FPC registries since the 1990s and several surveillance projects for high-risk individuals are now ongoing to detect early PCs. Improvement in lifestyle habits, including non-smoking, is recommended for individuals at risk. In Japan, the FPC study group was initiated in 2013 and the Japanese FPC registry was established in 2014 by the Japan Pancreas Society.

  6. Embryonic stem cell factors and pancreatic cancer.

    Science.gov (United States)

    Herreros-Villanueva, Marta; Bujanda, Luis; Billadeau, Daniel D; Zhang, Jin-San

    2014-03-07

    Pancreatic ductal adenocarcinoma (PDAC), the most common type of pancreatic tumor, is a highly aggressive human cancer with the lowest five-year survival rate of any human maligancy primarily due to its early- metastasis and lack of response to chemotherapy and radiation. Recent research suggests that PDAC cells comprise a hierarchy of tumor cells that develop around a population of cancer stem cells (CSCs), a small and distinct population of cancer cells that mediates tumoregenesis, metastasis and resistance to standard treatments. Thus, CSCs could be a target for more effective treatment options. Interestingly, pancreatic CSCs are subject to regulation by some of key embryonic stem cell (ESC) transctiption factors abberently expressed in PDAC, such as SOX2, OCT4 and NANOG. ESC transcription factors are important DNA-binding proteins present in both embryonic and adult somatic cells. The critical role of these factors in reprogramming processes makes them essential not only for embryonic development but also tumorigenesis. Here we provide an overview of stem cell transcription factors, particularly SOX2, OCT4, and NANOG, on their expression and function in pancreatic cancer. In contrast to embryonic stem cells, in which OCT4 and SOX2 are tightly regulated and physically interact to regulate a wide spectrum of target genes, de novo SOX2 expression alone in pancreatic cancer cells is sufficient to promote self-renewal, de-differentiation and imparting stemness characteristics via impacting specific cell cycle regulatory genes and epithelial-mesnechymal transtion driver genes. Thus, targeting ESC factors, particularly SOX2, could be a worthy strategy for pancreatic cancer therapy.

  7. Pancreatic cancer and depression: myth and truth

    Directory of Open Access Journals (Sweden)

    Schmid Roland M

    2010-10-01

    Full Text Available Abstract Background Various studies reported remarkable high incidence rates of depression in cancer patients compared with the general population. Pancreatic cancer is still one of the malignancies with the worst prognosis and therefore it seems quite logical that it is one of the malignancies with the highest incidence rates of major depression. However, what about the scientific background of this relationship? Is depression in patients suffering from pancreatic cancer just due to the confrontation with a life threatening disease and its somatic symptoms or is depression in this particular group of patients a feature of pancreatic cancer per se? Discussion Several studies provide evidence of depression to precede the diagnosis of pancreatic cancer and some studies even blame it for its detrimental influence on survival. The immense impact of emotional distress on quality of life of cancer patients enhances the need for its early diagnosis and adequate treatment. Knowledge about underlying pathophysiological mechanisms is required to provide the optimal therapy. Summary A review of the literature on this issue should reveal which are the facts and what is myth.

  8. Pan FGFR Kinase Inhibitor BGJ398 and Combination Chemotherapy in Treating Patients With Untreated Metastatic Pancreatic Cancer

    Science.gov (United States)

    2016-05-19

    Colon Adenocarcinoma; Metastatic Pancreatic Adenocarcinoma; Pancreatic Adenocarcinoma; Pancreatic Ductal Adenocarcinoma; Rectal Adenocarcinoma; Stage III Pancreatic Cancer; Stage IIIA Colon Cancer; Stage IIIA Rectal Cancer; Stage IIIB Colon Cancer; Stage IIIB Rectal Cancer; Stage IIIC Colon Cancer; Stage IIIC Rectal Cancer; Stage IV Pancreatic Cancer; Stage IVA Colon Cancer; Stage IVA Rectal Cancer; Stage IVB Colon Cancer; Stage IVB Rectal Cancer

  9. Imaging and Endoscopic Approaches to Pancreatic Cancer.

    Science.gov (United States)

    Rosenthal, Michael H; Lee, Alexander; Jajoo, Kunal

    2015-08-01

    Imaging and endoscopy both play important and complementary roles in the initial diagnosis, staging, monitoring, and symptomatic management of pancreatic cancer. This article provides an overview of the uses of each of the diagnostic modalities, common imaging findings, alternative considerations, and areas of ongoing work in diagnostic imaging. This article also provides details of the uses of endoscopy for diagnosis, staging, and intervention throughout the course of a patient's care. These modalities each play important roles in the complex multidisciplinary care of patients with pancreatic cancer.

  10. CXCL12 chemokine expression suppresses human pancreatic cancer growth and metastasis.

    Directory of Open Access Journals (Sweden)

    Ishan Roy

    Full Text Available Pancreatic ductal adenocarcinoma is an unsolved health problem with nearly 75% of patients diagnosed with advanced disease and an overall 5-year survival rate near 5%. Despite the strong link between mortality and malignancy, the mechanisms behind pancreatic cancer dissemination and metastasis are poorly understood. Correlative pathological and cell culture analyses suggest the chemokine receptor CXCR4 plays a biological role in pancreatic cancer progression. In vivo roles for the CXCR4 ligand CXCL12 in pancreatic cancer malignancy were investigated. CXCR4 and CXCR7 were consistently expressed in normal and cancerous pancreatic ductal epithelium, established cell lines, and patient-derived primary cancer cells. Relative to healthy exocrine ducts, CXCL12 expression was pathologically repressed in pancreatic cancer tissue specimens and patient-derived cell lines. To test the functional consequences of CXCL12 silencing, pancreatic cancer cell lines stably expressingthe chemokine were engineered. Consistent with a role for CXCL12 as a tumor suppressor, cells producing the chemokine wereincreasingly adherent and migration deficient in vitro and poorly metastatic in vivo, compared to control cells. Further, CXCL12 reintroduction significantly reduced tumor growth in vitro, with significantly smaller tumors in vivo, leading to a pronounced survival advantage in a preclinical model. Together, these data demonstrate a functional tumor suppressive role for the normal expression of CXCL12 in pancreatic ducts, regulating both tumor growth andcellulardissemination to metastatic sites.

  11. Leptomeningeal carcinomatosis as primary manifestation of pancreatic cancer.

    Science.gov (United States)

    Trinh, Victoria T; Medina-Flores, Rafael; Chohan, Muhammad O

    2016-08-01

    Leptomeningeal carcinomatosis (LMC) is a rare complication of cancer that often presents at an advanced stage after obvious metastasis of a primary cancer or locally advanced disease. We present an uncommon case of LMC secondary to pancreatic carcinoma presenting with headache, unilateral VII nerve palsy, and lower extremity weakness. Initial cerebrospinal fluid (CSF) studies were concerning for chronic aseptic meningitis but negative for malignant cells; the diagnosis of tuberculous meningitis was erroneously evoked. Three lumbar punctures were required to capture malignant cells. The diagnosis of LMC was based on CSF examination with cytology/immunohistochemistry and leptomeningeal enhancement on MRI. Post mortem autopsy revealed advanced and diffusely metastatic pancreatic adenocarcinoma. This patient demonstrates that solid tumors can present with leptomeningeal spread that often confuses the treating physician. Fungal or tuberculous meningitis can mimic LMC in the absence of neoplastic signs and negative CSF cytology. This event is exceedingly rare in pancreatic cancer. If the index of suspicion is high, repeat CSF sampling can increase the sensitivity of detection of malignant cells and thus result in the correct diagnosis.

  12. Various diffusion magnetic resonance imaging techniques for pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    Meng-Yue Tang; Xiao-Ming Zhang; Tian-Wu Chen; Xiao-Hua Huang

    2015-01-01

    Pancreatic cancer is one of the most common malignanttumors and remains a treatment-refractory cancer with a poor prognosis. Currently, the diagnosis of pancreatic neoplasm depends mainly on imaging and which methods are conducive to detecting small lesions. Compared to the other techniques, magnetic resonance imaging(MRI) has irreplaceable advantages and can provide valuable information unattainable with other noninvasive or minimally invasive imaging techniques. Advances in MR hardware and pulse sequence design have particularly improved the quality and robustness of MRI of the pancreas. Diffusion MR imaging serves as one of the common functional MRI techniques and is the only technique that can be used to reflect the diffusion movement of water molecules in vivo. It is generally known that diffusion properties depend on the characterization of intrinsic features of tissue microdynamics and microstructure. With the improvement of the diffusion models, diffusion MR imaging techniques are increasingly varied, from the simplest and most commonly used technique to the more complex. In this review, the various diffusion MRI techniques for pancreatic cancer are discussed, including conventional diffusion weighted imaging(DWI), multi-b DWI based on intra-voxel incoherent motion theory, diffusion tensor imaging and diffusion kurtosis imaging. The principles, main parameters, advantages and limitations of these techniques, as well as future directions for pancreatic diffusion imaging are also discussed.

  13. Circulating tumor DNA as a liquid biopsy target for detection of pancreatic cancer

    Science.gov (United States)

    Takai, Erina; Yachida, Shinichi

    2016-01-01

    Most pancreatic cancer patients present with advanced metastatic disease, resulting in extremely poor 5-year survival, mainly because of the lack of a reliable modality for early detection and limited therapeutic options for advanced disease. Therefore, there is a need for minimally-invasive diagnostic tools for detecting pancreatic cancer at an early stage, when curative surgery and also novel therapeutic approaches including precision medicine may be feasible. The “liquid biopsy” addresses these unmet clinical needs based on the concept that simple peripheral blood sampling and detection of circulating tumor DNA (ctDNA) could provide diagnostic information. In this review, we provide an overview of the current status of blood-based tests for diagnosis of pancreatic cancer and the potential utility of ctDNA for precision medicine. We also discuss challenges that remain to be addressed in developing practical ctDNA-based liquid biopsy approaches for early diagnosis of pancreatic cancer.

  14. Curcumin AntiCancer Studies in Pancreatic Cancer

    Science.gov (United States)

    Bimonte, Sabrina; Barbieri, Antonio; Leongito, Maddalena; Piccirillo, Mauro; Giudice, Aldo; Pivonello, Claudia; de Angelis, Cristina; Granata, Vincenza; Palaia, Raffaele; Izzo, Francesco

    2016-01-01

    Pancreatic cancer (PC) is one of the deadliest cancers worldwide. Surgical resection remains the only curative therapeutic treatment for this disease, although only the minority of patients can be resected due to late diagnosis. Systemic gemcitabine-based chemotherapy plus nab-paclitaxel are used as the gold-standard therapy for patients with advanced PC; although this treatment is associated with a better overall survival compared to the old treatment, many side effects and poor results are still present. Therefore, new alternative therapies have been considered for treatment of advanced PC. Several preclinical studies have demonstrated that curcumin, a naturally occurring polyphenolic compound, has anticancer effects against different types of cancer, including PC, by modulating many molecular targets. Regarding PC, in vitro studies have shown potent cytotoxic effects of curcumin on different PC cell lines including MiaPaCa-2, Panc-1, AsPC-1, and BxPC-3. In addition, in vivo studies on PC models have shown that the anti-proliferative effects of curcumin are caused by the inhibition of oxidative stress and angiogenesis and are due to the induction of apoptosis. On the basis of these results, several researchers tested the anticancer effects of curcumin in clinical trials, trying to overcome the poor bioavailability of this agent by developing new bioavailable forms of curcumin. In this article, we review the results of pre-clinical and clinical studies on the effects of curcumin in the treatment of PC. PMID:27438851

  15. Curcumin AntiCancer Studies in Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Sabrina Bimonte

    2016-07-01

    Full Text Available Pancreatic cancer (PC is one of the deadliest cancers worldwide. Surgical resection remains the only curative therapeutic treatment for this disease, although only the minority of patients can be resected due to late diagnosis. Systemic gemcitabine-based chemotherapy plus nab-paclitaxel are used as the gold-standard therapy for patients with advanced PC; although this treatment is associated with a better overall survival compared to the old treatment, many side effects and poor results are still present. Therefore, new alternative therapies have been considered for treatment of advanced PC. Several preclinical studies have demonstrated that curcumin, a naturally occurring polyphenolic compound, has anticancer effects against different types of cancer, including PC, by modulating many molecular targets. Regarding PC, in vitro studies have shown potent cytotoxic effects of curcumin on different PC cell lines including MiaPaCa-2, Panc-1, AsPC-1, and BxPC-3. In addition, in vivo studies on PC models have shown that the anti-proliferative effects of curcumin are caused by the inhibition of oxidative stress and angiogenesis and are due to the induction of apoptosis. On the basis of these results, several researchers tested the anticancer effects of curcumin in clinical trials, trying to overcome the poor bioavailability of this agent by developing new bioavailable forms of curcumin. In this article, we review the results of pre-clinical and clinical studies on the effects of curcumin in the treatment of PC.

  16. Cancer surveillance of patients from familial pancreatic cancer kindreds.

    Science.gov (United States)

    Brentnall, T A

    2000-05-01

    The family history can be used to determine which family members warrant surveillance and when to start it. Surveillance should be started at least 1 decade before the earliest age of pancreatic cancer in the family. EUS is the basic, least-invasive surveillance tool; however, findings are similar to those seen in chronic pancreatitis. All patients who have a positive EUS or who have symptoms warrant ERCP. Changes on ERCP of ductal stricturing and clubbed or saccular side branches are suggestive of patients who may need pancreatectomy in the setting of hereditary pancreatic cancer. The goal for surveillance of familial pancreatic cancer patients is to diagnose them before the development of cancer, when they have dysplasia or carcinoma in situ, and to perform a complete pancreatectomy. Timing is crucial for determining when a patient warrants surgery; if performed too early, the patient is put at risk for the morbidity and mortality of a total pancreatectomy, which is not inconsequential. If the patient survives the operation, he or she is often left a brittle diabetic. The alternative of diagnosing too late is more worrisome because the patient dies of pancreatic cancer. An essential ingredient to a good patient outcome is a team approach to these patients, using gastroenterologists, surgeons, and pathologists who have expertise and interest in pancreatic disease.

  17. Stereotactic body radiation therapy planning with duodenal sparing using volumetric-modulated arc therapy vs intensity-modulated radiation therapy in locally advanced pancreatic cancer: A dosimetric analysis

    Energy Technology Data Exchange (ETDEWEB)

    Kumar, Rachit; Wild, Aaron T.; Ziegler, Mark A.; Hooker, Ted K.; Dah, Samson D.; Tran, Phuoc T.; Kang, Jun; Smith, Koren; Zeng, Jing [Department of Radiation Oncology and Molecular Radiation Sciences, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Hospital, 401N. Broadway, Weinberg Suite 1440, Baltimore, MD 21231 (United States); Pawlik, Timothy M. [Department of Surgery, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD (United States); Tryggestad, Erik [Department of Radiation Oncology and Molecular Radiation Sciences, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Hospital, 401N. Broadway, Weinberg Suite 1440, Baltimore, MD 21231 (United States); Ford, Eric [Department of Radiation Oncology, Fred Hutchinson Cancer Center, University of Washington, Seattle, WA (United States); Herman, Joseph M., E-mail: jherma15@jhmi.edu [Department of Radiation Oncology and Molecular Radiation Sciences, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Hospital, 401N. Broadway, Weinberg Suite 1440, Baltimore, MD 21231 (United States)

    2013-10-01

    Stereotactic body radiation therapy (SBRT) achieves excellent local control for locally advanced pancreatic cancer (LAPC), but may increase late duodenal toxicity. Volumetric-modulated arc therapy (VMAT) delivers intensity-modulated radiation therapy (IMRT) with a rotating gantry rather than multiple fixed beams. This study dosimetrically evaluates the feasibility of implementing duodenal constraints for SBRT using VMAT vs IMRT. Non–duodenal sparing (NS) and duodenal-sparing (DS) VMAT and IMRT plans delivering 25 Gy in 1 fraction were generated for 15 patients with LAPC. DS plans were constrained to duodenal D{sub max} of<30 Gy at any point. VMAT used 1 360° coplanar arc with 4° spacing between control points, whereas IMRT used 9 coplanar beams with fixed gantry positions at 40° angles. Dosimetric parameters for target volumes and organs at risk were compared for DS planning vs NS planning and VMAT vs IMRT using paired-sample Wilcoxon signed rank tests. Both DS VMAT and DS IMRT achieved significantly reduced duodenal D{sub mean}, D{sub max}, D{sub 1cc}, D{sub 4%}, and V{sub 20} {sub Gy} compared with NS plans (all p≤0.002). DS constraints compromised target coverage for IMRT as demonstrated by reduced V{sub 95%} (p = 0.01) and D{sub mean} (p = 0.02), but not for VMAT. DS constraints resulted in increased dose to right kidney, spinal cord, stomach, and liver for VMAT. Direct comparison of DS VMAT and DS IMRT revealed that VMAT was superior in sparing the left kidney (p<0.001) and the spinal cord (p<0.001), whereas IMRT was superior in sparing the stomach (p = 0.05) and the liver (p = 0.003). DS VMAT required 21% fewer monitor units (p<0.001) and delivered treatment 2.4 minutes faster (p<0.001) than DS IMRT. Implementing DS constraints during SBRT planning for LAPC can significantly reduce duodenal point or volumetric dose parameters for both VMAT and IMRT. The primary consequence of implementing DS constraints for VMAT is increased dose to other organs at

  18. TU-CD-BRB-08: Radiomic Analysis of FDG-PET Identifies Novel Prognostic Imaging Biomarkers in Locally Advanced Pancreatic Cancer Patients Treated with SBRT

    Energy Technology Data Exchange (ETDEWEB)

    Cui, Y; Shirato, H [Hokkaido University, Global Institute for Collaborative Research and Educat, Sapporo, Hokkaido (Japan); Song, J; Pollom, E; Chang, D; Koong, A [Stanford University, Palo Alto, CA (United States); Li, R [Hokkaido University, Global Institute for Collaborative Research and Educat, Sapporo, Hokkaido (Japan); Stanford University, Palo Alto, CA (United States)

    2015-06-15

    Purpose: This study aims to identify novel prognostic imaging biomarkers in locally advanced pancreatic cancer (LAPC) using quantitative, high-throughput image analysis. Methods: 86 patients with LAPC receiving chemotherapy followed by SBRT were retrospectively studied. All patients had a baseline FDG-PET scan prior to SBRT. For each patient, we extracted 435 PET imaging features of five types: statistical, morphological, textural, histogram, and wavelet. These features went through redundancy checks, robustness analysis, as well as a prescreening process based on their concordance indices with respect to the relevant outcomes. We then performed principle component analysis on the remaining features (number ranged from 10 to 16), and fitted a Cox proportional hazard regression model using the first 3 principle components. Kaplan-Meier analysis was used to assess the ability to distinguish high versus low-risk patients separated by median predicted survival. To avoid overfitting, all evaluations were based on leave-one-out cross validation (LOOCV), in which each holdout patient was assigned to a risk group according to the model obtained from a separate training set. Results: For predicting overall survival (OS), the most dominant imaging features were wavelet coefficients. There was a statistically significant difference in OS between patients with predicted high and low-risk based on LOOCV (hazard ratio: 2.26, p<0.001). Similar imaging features were also strongly associated with local progression-free survival (LPFS) (hazard ratio: 1.53, p=0.026) on LOOCV. In comparison, neither SUVmax nor TLG was associated with LPFS (p=0.103, p=0.433) (Table 1). Results for progression-free survival and distant progression-free survival showed similar trends. Conclusion: Radiomic analysis identified novel imaging features that showed improved prognostic value over conventional methods. These features characterize the degree of intra-tumor heterogeneity reflected on FDG

  19. Review of screening for pancreatic cancer in high risk individuals

    OpenAIRE

    Stoita, Alina; Penman, Ian D; Williams, David B.

    2011-01-01

    Pancreatic cancer is difficult to diagnose at an early stage and is associated with a very poor survival. Ten percent of pancreatic cancers result from genetic susceptibility and/or familial aggregation. Individuals from families with multiple affected first-degree relatives and those with a known cancer-causing genetic mutation have been shown to be at much higher risk of developing pancreatic cancer. Recent efforts have focused on detecting disease at an earlier stage to improve survival in...

  20. Reactive Oxygen Species and Targeted Therapy for Pancreatic Cancer

    OpenAIRE

    Lun Zhang; Jiahui Li; Liang Zong; Xin Chen; Ke Chen; Zhengdong Jiang; Ligang Nan; Xuqi Li; Wei Li; Tao Shan; Qingyong Ma; Zhenhua Ma

    2016-01-01

    Pancreatic cancer is the fourth leading cause of cancer-related death in the United States. Reactive oxygen species (ROS) are generally increased in pancreatic cancer cells compared with normal cells. ROS plays a vital role in various cellular biological activities including proliferation, growth, apoptosis, and invasion. Besides, ROS participates in tumor microenvironment orchestration. The role of ROS is a doubled-edged sword in pancreatic cancer. The dual roles of ROS depend on the concent...

  1. Increased pancreatic cancer risk following radiotherapy for testicular cancer

    DEFF Research Database (Denmark)

    Hauptmann, Michael; Børge Johannesen, Tom; Gilbert, Ethel S

    2016-01-01

    BACKGROUND: Pancreatic cancer risk is elevated among testicular cancer (TC) survivors. However, the roles of specific treatments are unclear. METHODS: Among 23 982 5-year TC survivors diagnosed during 1947-1991, doses from radiotherapy to the pancreas were estimated for 80 pancreatic cancer...... patients and 145 matched controls. Chemotherapy details were recorded. Logistic regression was used to estimate odds ratios (ORs). RESULTS: Cumulative incidence of second primary pancreatic cancer was 1.1% at 30 years after TC diagnosis. Radiotherapy (72 (90%) cases and 115 (80%) controls) was associated...... with the number of cycles of chemotherapy with alkylating or platinum agents (P=0.057), although only one case was exposed to platinum. CONCLUSIONS: A dose-response relationship exists between radiation to the pancreas and subsequent cancer risk, and persists for over 20 years. These excesses, although small...

  2. Met receptor tyrosine kinase signaling induces secretion of the angiogenic chemokine interleukin-8/CXCL8 in pancreatic cancer.

    Directory of Open Access Journals (Sweden)

    Kristen S Hill

    Full Text Available At diagnosis, the majority of pancreatic cancer patients present with advanced disease when curative resection is no longer feasible and current therapeutic treatments are largely ineffective. An improved understanding of molecular targets for effective intervention of pancreatic cancer is thus urgent. The Met receptor tyrosine kinase is one candidate implicated in pancreatic cancer. Notably, Met is over expressed in up to 80% of invasive pancreatic cancers but not in normal ductal cells correlating with poor overall patient survival and increased recurrence rates following surgical resection. However the functional role of Met signaling in pancreatic cancer remains poorly understood. Here we used RNA interference to directly examine the pathobiological importance of increased Met signaling for pancreatic cancer. We show that Met knockdown in pancreatic tumor cells results in decreased cell survival, cell invasion, and migration on collagen I in vitro. Using an orthotopic model for pancreatic cancer, we provide in vivo evidence that Met knockdown reduced tumor burden correlating with decreased cell survival and tumor angiogenesis, with minimal effect on cell growth. Notably, we report that Met signaling regulates the secretion of the pro-angiogenic chemokine interleukin-8/CXCL8. Our data showing that the interleukin-8 receptors CXCR1 and CXCR2 are not expressed on pancreatic tumor cells, suggests a paracrine mechanism by which Met signaling regulates interleukin-8 secretion to remodel the tumor microenvironment, a novel finding that could have important clinical implications for improving the effectiveness of treatments for pancreatic cancer.

  3. RISK FACTORS FOR PANCREATIC CANCER: UNDERLYING MECHANISMS AND POTENTIAL TARGETS

    Directory of Open Access Journals (Sweden)

    Thomas eKolodecik

    2014-01-01

    Full Text Available Purpose of the review:Pancreatic cancer is extremely aggressive, forming highly chemo-resistant tumors, and has one of the worst prognoses. The evolution of this cancer is multi-factorial. Repeated acute pancreatic injury and inflammation are important contributing factors in the development of pancreatic cancer. This article attempts to understand the common pathways linking pancreatitis to pancreatic cancer.Recent Findings:Intracellular activation of both pancreatic enzymes and the transcription factor NF-kB are important mechanisms that induce acute pancreatitis. Recurrent pancreatic injury due to genetic susceptibility, environmental factors such as smoking, alcohol intake, and conditions such as obesity lead to increases in oxidative stress, impaired autophagy and constitutive activation of inflammatory pathways. These processes can stimulate pancreatic stellate cells, thereby increasing fibrosis and encouraging chronic disease development. Activation of oncogneic Kras mutations through inflammation, coupled with altered levels of tumor suppressor proteins (p53 and p16 can ultimately lead to development of pancreatic cancer. Summary:Although our understanding of pancreatitis and pancreatic cancer has tremendously increased over many years, much remains to be elucidated in terms of common pathways linking these conditions.

  4. Pancreatic stellate cells promote epithelial-mesenchymal transition in pancreatic cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Kikuta, Kazuhiro [Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai (Japan); Masamune, Atsushi, E-mail: amasamune@med.tohoku.ac.jp [Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai (Japan); Watanabe, Takashi; Ariga, Hiroyuki; Itoh, Hiromichi; Hamada, Shin; Satoh, Kennichi [Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai (Japan); Egawa, Shinichi; Unno, Michiaki [Department of Hepatobiliary-Pancreatic Surgery, Tohoku University Graduate School of Medicine, Sendai (Japan); Shimosegawa, Tooru [Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai (Japan)

    2010-12-17

    Research highlights: {yields} Recent studies have shown that pancreatic stellate cells (PSCs) promote the progression of pancreatic cancer. {yields} Pancreatic cancer cells co-cultured with PSCs showed loose cell contacts and scattered, fibroblast-like appearance. {yields} PSCs decreased the expression of epithelial markers but increased that of mesenchymal markers, along with increased migration. {yields} This study suggests epithelial-mesenchymal transition as a novel mechanism by which PSCs contribute to the aggressive behavior of pancreatic cancer cells. -- Abstract: The interaction between pancreatic cancer cells and pancreatic stellate cells (PSCs), a major profibrogenic cell type in the pancreas, is receiving increasing attention. There is accumulating evidence that PSCs promote the progression of pancreatic cancer by increasing cancer cell proliferation and invasion as well as by protecting them from radiation- and gemcitabine-induced apoptosis. Because epithelial-mesenchymal transition (EMT) plays a critical role in the progression of pancreatic cancer, we hypothesized that PSCs promote EMT in pancreatic cancer cells. Panc-1 and SUIT-2 pancreatic cancer cells were indirectly co-cultured with human PSCs isolated from patients undergoing operation for pancreatic cancer. The expression of epithelial and mesenchymal markers was examined by real-time PCR and immunofluorescent staining. The migration of pancreatic cancer cells was examined by scratch and two-chamber assays. Pancreatic cancer cells co-cultured with PSCs showed loose cell contacts and a scattered, fibroblast-like appearance. The expression of E-cadherin, cytokeratin 19, and membrane-associated {beta}-catenin was decreased, whereas vimentin and Snail (Snai-1) expression was increased more in cancer cells co-cultured with PSCs than in mono-cultured cells. The migration of pancreatic cancer cells was increased by co-culture with PSCs. The PSC-induced decrease of E-cadherin expression was not altered

  5. How fibrosis influences imaging and surgical decisions in pancreatic cancer

    Directory of Open Access Journals (Sweden)

    Mert eErkan

    2012-10-01

    Full Text Available Our understanding of pancreatic ductal adenocarcinoma is shifting away from a disease of malignant ductal cells-only, towards a complex system where tumor evolution is a result of interaction of cancer cells with their microenvironment. This change has led to intensification of research focusing on the fibrotic stroma of pancreatic ductal adenocarcinoma. Pancreatic stellate cells are the main fibroblastic cells of the pancreas which are responsible for producing the desmoplasia in chronic pancreatitis and pancreatic ductal adenocarcinoma. Clinically, the effect of desmoplasia is two-sided; on the negative side it is a hurdle in the diagnosis of pancreatic ductal adenocarcinoma because the fibrosis in cancer resembles that of chronic pancreatitis. It is also believed that pancreatic stellate cells and pancreatic fibrosis are partially responsible for the therapy resistance in pancreatic cancer. On the positive side, a fibrotic pancreas is safer to operate on compared to a fatty and soft pancreas which is prone for postoperative pancreatic fistula. In this review the impact of pancreatic fibrosis on diagnosis of pancreatic cancer and surgical decisions are discussed from a clinical point of view.

  6. Tumor antigens as related to pancreatic cancer.

    Science.gov (United States)

    Chu, T M; Holyoke, E D; Douglass, H O

    1980-01-01

    Data are presented suggesting the presence of pancreas tumor-associated antigens. Slow progress has been made during the past few years in the identification of pancreatic tumor antigens that may be of clinical usefulness and it seems unlikely that many of the practical problems now being faced in identification and isolation of these antigens and in development of a specific, sensitive assay will be solved by conventional immunochemical approaches. The study of antigen and/or antibody purified from immune complexes in the host and the application of leukocyte adherence inhibition techniques to immunodiagnosis of pancreatic cancer are among the new approaches that may provide effective alternatives in the study of pancreatic tumor antigens.

  7. Pancreatic Cancer Epidemiology, Detection, and Management

    Directory of Open Access Journals (Sweden)

    Qiubo Zhang

    2016-01-01

    Full Text Available PC (pancreatic cancer is the fourth most common cause of death due to cancer worldwide. The incidence and mortality rates have been increasing year by year worldwide, and this review has analyzed the most recent incidence and mortality data for pancreatic cancer occurrence in China. Several possible risk factors have been discussed here, involving known established risk factors and novel possible risk factors. The development of this cancer is a stepwise progression through intraepithelial neoplasia to carcinoma. Though early and accurate diagnosis is promising based on a combination of recent techniques including tumor markers and imaging modalities, lacking early clinical symptoms makes the diagnosis late. Correct staging is critical because treatment is generally based on this parameter. Treatment options have improved throughout the last decades. However, surgical excision remains the primary therapy and efficacy of conventional chemoradiotherapy for PC is limited. Recently, some novel new therapies have been developed and will be applied in clinics soon. This review will provide an overview of pancreatic cancer, including an understanding of the developments and controversies.

  8. Indicative findings of pancreatic cancer in prediagnostic CT

    Energy Technology Data Exchange (ETDEWEB)

    Ahn, Sung Soo; Choi, Jin-Young; Hong, Hye-Suk; Chung, Yong Eun; Lim, Joon Seok [Yonsei University College of Medicine, Department of Diagnostic Radiology, Research Institute of Radiological Science, Severance Hospital, Seoul (Korea); Kim, Myeong-Jin [Yonsei University College of Medicine, Department of Diagnostic Radiology, Research Institute of Radiological Science, Severance Hospital, Seoul (Korea); Yonsei University College of Medicine, Institute of Gastroenterology and Brain Korea 21 project, Seoul (Korea); Department of Radiology, Severance Hospital, Yonsei University College of Medicine, Seoul (Korea)

    2009-10-15

    We examined 20 prediagnostic CTs from 16 patients for whom the diagnosis of pancreatic cancer was delayed until full diagnostic CT was performed. Three radiologists independently reviewed the prediagnostic CTs along with 50 CTs of control subjects, including patients without pancreatic disease (n = 38) or with chronic pancreatitis without calcification visible on CT (n=12). The reviewers recorded the presence of biliary or pancreatic ductal dilation, interruption of the pancreatic duct, distal parenchymal atrophy, contour abnormality and focal hypoattenuation. Frequency, sensitivity and specificity of the significant findings were calculated. Logistic regression analysis was performed. Findings indicative of pancreatic cancer were seen on 85% (17/20) of the prediagnostic CTs. Patients with pancreatic cancer were significantly (p<0.05) more likely to show focal hypoattenuation, pancreatic duct dilation, interruption of the pancreatic duct, and distal parenchymal atrophy, with sensitivities and specificities of 75%/84%, 50%/78%, 45%/82% and 45%/96%, respectively. Focal hypoattenuation and distal parenchymal atrophy were the independent predictors of pancreatic cancer with odds ratios of 20.92 and 11.22, respectively. In conclusion, focal hypoattenuation and pancreatic duct dilation with or without interruption, especially when accompanied by distal parenchymal atrophy, were the most useful findings for avoiding delayed diagnosis of pancreatic cancer. (orig.)

  9. Evaluation of Trace Elements in Pancreatic Cancer Patients in Iran

    Directory of Open Access Journals (Sweden)

    Leila Farzin

    2013-04-01

    Full Text Available Background: Pancreatic cancer is a major worldwide health problem. Little is known about the etiology of pancreatic cancer, which is an important cause of cancer mortality in developed countries. This study evaluates the importance of amounts of trace elements in pancreatic cancer etiology and diagnostics.Methods: Atomic absorption spectrometry was used to estimate zinc, selenium, copper, cadmium and lead concentrations in 80 patients with pancreatic cancer admitted to various hospitals in Tehran Province over an 18-month period and in 100 control subjects.Results: There were significantly lower levels (P0.05.Conclusion: In this study and by analyzing data from recent major reported series, we have found that cadmium is a plausible pancreatic carcinogen. This study also suggests a significant relationship between zinc metabolism and pancreatic cancer.

  10. Gemcitabine Hydrochloride With or Without Erlotinib Hydrochloride Followed By the Same Chemotherapy Regimen With or Without Radiation Therapy and Capecitabine or Fluorouracil in Treating Patients With Pancreatic Cancer That Has Been Removed By Surgery

    Science.gov (United States)

    2016-10-19

    Pancreatic Acinar Cell Carcinoma; Pancreatic Ductal Adenocarcinoma; Pancreatic Intraductal Papillary-Mucinous Neoplasm; Stage IA Pancreatic Cancer; Stage IB Pancreatic Cancer; Stage IIA Pancreatic Cancer; Stage IIB Pancreatic Cancer

  11. Ultrasound-enhanced nanotherapy of pancreatic cancer

    Science.gov (United States)

    Rapoport, N.; Nam, K.-H.; Christensen, D. A.; Kennedy, A. M.; Shea, J. E.; Scaife, C. L.

    2010-03-01

    The paper reports in vivo results of ultrasonic nanotherapy of orthotopically grown pancreatic cancer. Phase-shift paclitaxel (PTX) loaded perfluoropentane (PFP) nanoemusions combined with tumor-directed ultrasound have been used with a considerable success for tumor-targeted chemotherapy of gemcitabin (GEM)-refractory pancreatic cancer (PC). The GEM-resistant pancreatic cancer proved sensitive to treatment by a micellar PTX formulation Genexol PM (GEN) andor nanodroplet PTX formulation ndGEN. Due to increased permeability of tumor blood vessels, drug-loaded nanodroplets accumulated in the tumor via passive targeting, which was confirmed by ultrasound imaging. Nanodroplets converted into microbubbles in situ under the action of tumor-directed 1-MHz therapeutic ultrasound. The strongest therapeutic effect was observed for the combination therapy by PTX-loaded nanodroplets, GEM and ultrasound (ndGEN+GEM+ultrasound). This combination therapy resulted in a spectacular tumor regression and in some cases complete tumor resolution. Moreover, formation of metastases was dramatically decreased and ascitis generation was completely suppressed. However for all animal groups, local tumor recurrence was observed after the completion of the treatment indicating that some cancer cells survived the treatment. The recurrent tumors proved more resistant to the repeated therapy than initial tumors.

  12. Aberrant expression of Wnt antagonist SFRP1 in pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    BU Xian-min; ZHAO Cheng-hai; DAI Xian-wei

    2008-01-01

    @@ Pancreatic cancer is one of the malignant tumor with a very poor prognosis. Both genetic and epigenetic alterations are involved in the pathogenetic mechanisms of pancreatic cancer. Hypermethylation and subsequent loss of expression of some tumor suppressor genes and tumor-related genes occur frequently in pancreatic cancer, such as loss of expression of pl6,1 RASSF1A,2 SOCS-1,3 and hMLH14 genes were repoted.

  13. Pancreatic cancer cachexia: A review of mechanisms and therapeutics

    Directory of Open Access Journals (Sweden)

    Carlyn Rose Tan

    2014-03-01

    Full Text Available Over the last decade, we have gained new insight into the pathophysiology of pancreatic cancer cachexia. Unfortunately, its treatment is complex and remains a challenge. Pancreatic cancer cachexia is a multifactorial syndrome characterized by uncompensated adipose tissue and skeletal muscle loss in the setting of anorexia that leads to progressive functional impairment. This paper will review the current concepts of pancreatic cancer cachexia, its assessment and pathophysiology as well as current and future treatments. The successful management of pancreatic cancer cachexia will likely require a multimodal approach that includes nutritional support and combination pharmaceutical interventions.

  14. Disseminated tumor cells in pancreatic cancer-an independent prognosticator of disease progression and survival

    NARCIS (Netherlands)

    Effenberger, Katharina E.; Schroeder, Cornelia; Eulenburg, Christine; Reeh, Matthias; Tachezy, Michael; Riethdorf, Sabine; Vashist, Yogesh K.; Izbicki, Jakob R.; Pantel, Klaus; Bockhorn, Maximilian

    2012-01-01

    Pancreatic cancer is one of the most devastating cancers with a 6-month median survival and a 5-year survival rate of 35%. Still important aspects of its aggressive biology remain elusive and advanced therapeutic regimens have not been substantially successful. We investigated the prognostic role of

  15. Synergistic activity of troxacitabine (Troxatyl™ and gemcitabine in pancreatic cancer

    Directory of Open Access Journals (Sweden)

    Leblond Lorraine

    2007-07-01

    Full Text Available Abstract Background Gemcitabine, a deoxycytidine nucleoside analog, is the current standard chemotherapy used as first-line treatment for patients with locally advanced or metastatic cancer of the pancreas, and extends life survival by 5.7 months. Advanced pancreatic cancer thus remains a highly unmet medical need and new therapeutic agents are required for this patient population. Troxacitabine (Troxatyl™ is the first unnatural L-nucleoside analog to show potent preclinical antitumor activity and is currently under clinical investigation. Troxacitabine was recently evaluated as a first-line therapy in 54 patients with advanced adenocarcinoma of the pancreas and gave comparable overall results to those reported with gemcitabine in recently published randomized trials. Methods The human pancreatic adenocarcinoma cell lines, AsPC-1, Capan-2, MIA PaCa-2 and Panc-1, were exposed to troxacitabine or gemcitabine alone or in combination, for 72 h, and the effects on cell growth were determined by electronic particle counting. Synergistic efficacy was determined by the isobologram and combination-index methods of Chou and Talalay. Mechanistic studies addressed incorporation of troxacitabine into DNA and intracellular levels of troxacitabine and gemcitabine metabolites. For in vivo studies, we evaluated the effect of both drugs, alone and in combination, on the growth of established human pancreatic (AsPC-1 tumors implanted subcutaneously in nude mice. Statistical analysis was calculated by a one-way ANOVA with Dunnett as a post-test and the two-tailed unpaired t test using GraphPad prism software. Results Synergy, evaluated using the CalcuSyn Software, was observed in all four cell-lines at multiple drug concentrations resulting in combination indices under 0.7 at Fa of 0.5 (50% reduction of cell growth. The effects of drug exposures on troxacitabine and gemcitabine nucleotide pools were analyzed, and although gemcitabine reduced phosphorylation of

  16. Value of ultrasound examination in differential diagnosis of pancreatic lymphoma and pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    Li Qiu; Yan Luo; Yu-Lan Peng

    2008-01-01

    AIM:To investigate the value of clinical manifestations and ultrasound examination in the differential diagnosis of pancreatic lymphoma and pancreatic cancer.METHODS:The clinical and ultrasonic characteristics of 12 cases of pancreatic lymphoma and 30 cases of pancreatic cancer were retrospectively analyzed.RESULTS:Statistically significant differences were found in the course of disease,back pain,jaundice,carcino-embryonic antigen (CEA) and CA19-9 increase,palpable abdominal lump,superficial lymph node enlargement,fever and night sweats,lesion size,bile duct expansion,pancreatic duct expansion,vascular involvement,retroperitoneal (below the renal vein level)lymph node enlargement,and intrahepatic metastasis between pancreatic lymphoma and pancreatic cancer.There were no significant differences in age of onset,gender ratio,weight loss,nausea and vomiting,lesion position,the echo of the lesion,and the blood flow of the lesion.CONCLUSION:Pancreatic lymphoma should be considered for patients with long lasting symptoms,superficial lymph node enlargement,palpable abdominal lump,fever and night sweats,relatively large lesions,and retroperitoneal (below the level of the renal vein) lymph node enlargement.A diagnosis of pancreatic cancer should be considered more likely in the patients with relatively short disease course,jaundice,back pain,CEA and CA19-9 increase,relatively small lesions,bile duct expansion,obvious pancreatic duct expansion,peripheral vascular wrapping and involvement,or intrahepatic metastases.

  17. Enteric duplication cyst of the pancreas associated with chronic pancreatitis and pancreatic cancer.

    Science.gov (United States)

    Chiu, Alexander S; Bluhm, David; Xiao, Shu-Yan; Waxman, Irving; Matthews, Jeffrey B

    2014-05-01

    Pancreas-associated enteric duplication cysts are rare developmental anomalies that communicate with the main pancreatic duct and may be associated with recurrent acute and chronic abdominal pain in children. In adults, these lesions may masquerade as pancreatic pseudocysts or pancreatic cystic neoplasms. An adult patient with a pancreas-associated enteric duplication is described which represents the first reported instance of association with both chronic calcific pancreatitis and pancreatic cancer. The clinical spectrum of pancreas-associated enteric duplication cyst, including diagnostic and therapeutic options, is reviewed.

  18. How to improve the early diagnosis of pancreatic cancer%如何提高胰腺癌的早期诊断率

    Institute of Scientific and Technical Information of China (English)

    张太平; 展翰翔; 赵玉沛

    2009-01-01

    Pancreatic cancer is highly malignant with a poor prognosis. The resectability and prognosis of early pancreatic cancer are much better than the advanced, so early diagnosis is crucial for saving patients' lives. Because the symptoms of pancreatic cancer are non-specific, most of the patients are misdiagnosed as gastrointestinal or hepatobiliary diseases. Early diagnosis rate of pancreatic cancer can be greatly improved by combined application of tumor marker detection, endoscopic ultrasound, computed tomography, positron emission tomo-graphy, and etc. Early screening of high-risk population has been advocated by the experts, and its value in early diagnosis of pancreatic cancer has been confirmed by relevant studies. The colaboration of multiple pancreatic surgery centers in conducting prospective studies and setting gnidlines for the pancreatic cancer diagnosis, and relevant fundamental reseaches should also be emphasized.

  19. Small Intestine Bacterial Overgrowth: An Underdiagnosed Cause of Diarrhea in Patients with Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Ivan Bustillo

    2009-09-01

    Full Text Available Dear Sir: Pancreatic cancer is currently the fourth leading cause of cancer related death in the United States, with an overall survival rate at five years of diagnosis of less than 5%. It affects more men than women, with slight preponderance for African Americans and 77% of patients are diagnosed after the age of 60 years [1]. The majority of patients with advanced pancreatic cancer report a poor quality of life, with special compromise in the areas of emotional and social functioning, presumably due to anxiety and depression [2]. Among the physical symptoms reported to affect quality of life, fatigue and pain were ranked the highest. However, we are yet to understand how other less commonly recognized symptoms such as diarrhea and weight loss affect the functioning and comfort level of these patients. Small intestine bacterial overgrowth is a frequent, yet unrecognized, cause of diarrhea in patients with advanced pancreatic cancer.

  20. Pancreas duodenal homeobox-1 expression and significance in pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    Tao Liu; Shan-Miao Gou; Chun-You Wang; He-Shui Wu; Jiong-Xin Xiong; Feng Zhou

    2007-01-01

    AIM: To study the correlations of Pancreas duodenal homeobox-1 with pancreatic cancer characteristics,incluling pathological grading, TNM grading, tumor metastasis and tumor cell proliferation.METHODS: Reverse transcriptase-polymerase chain reaction (RT-PCR) was used to detect PDX-1 mRNA expression in pancreatic cancer tissue and normal pancreatic tissue. The expression of PDX-1 protein was measured by Western blot and immunohistochemistry.Immunohistochemistry was also used to detect proliferative cell nuclear antigen (PCNA). Correlations of PDX-1 with pancreatic cancer characteristics, including pathological grading, TNM grading, tumor metastasis and tumor cell proliferation, were analyzed by using χ2 test.RESULTS: Immunohistochemistry showed that 41.1% of pancreatic cancers were positive for PDX-1 expression,but normal pancreatic tissue except islets showed no staining for PDX-1. In consistent with the result of imunohistochemistry, Western blot showed that 37.5% of pancreatic cancers were positive for PDX-1. RT-PCR showed that PDX-1 expression was significantly higher in pancreatic cancer tissues than normal pancreatic tissues (2-3.56 ± 0.35 vs 2-8.76 ± 0.14, P< 0.01). Lymph node metastasis (P < 0.01), TNM grading (P < 0.05), pathological grading (P < 0.05) and tumor cell proliferation (P < 0.01) were significantly correlated with PDX-1 expression levels.CONCLUSION: PDX-1 is re-expressed in pancreatic cancer, and PDX-1-positive pancreatic cancer cells show more malignant potential compared to PDX-1-negative cells. Therefore, PDX-1-positive cells may be tumor stem cells and PDX-1 may act as alternate surface marker of pancreatic cancer stem cells.

  1. Dendritic cell-based vaccine for pancreatic cancer in Japan

    Institute of Scientific and Technical Information of China (English)

    Masato Okamoto; Masanori Kobayashi; Yoshikazu Yonemitsu; Shigeo Koido; Sadamu Homma

    2016-01-01

    "Vaccell" is a dendritic cell(DC)-based cancer vaccine which has been established in Japan. The DCs play central roles in deciding the direction of host immune reactions as well as antigen presentation. We have demonstrated that DCs treated with a streptococcal immune adjuvant OK-432, produce interleukin-12, induce Th1-dominant state, and elicit anti-tumor effects, more powerful than those treated with the known DCmaturating factors. We therefore decided to mature DCs by the OK-432 for making an effective DC vaccine, Vaccell. The 255 patients with inoperable pancreatic cancer who received standard chemotherapy combined with DC vaccines, were analyzed retrospectively. Survival time of the patients with positive delayed type hypersensitivity(DTH) skin reaction was significantly prolonged as compared with that of the patients with negative DTH. The findings strongly suggest that there may be "Responders" for the DC vaccine in advanced pancreatic cancer patients. We next conducted a smallscale prospective clinical study. In this trial, we pulsed HLA class Ⅱ-restricted WT1 peptide(WT1-Ⅱ) in addition to HLA class Ⅰ-restricted peptide(WT1-Ⅰ) into the DCs. Survival of the patients received WT1-Ⅰ and-Ⅱ pulsed DC vaccine was significantly extended as compared to that of the patients received DCs pulsed with WT1-Ⅰ or WT1-Ⅱ alone. Furthermore, WT1-specific DTH positive patients showed significantly improved the overall survival as well as progressionfree survival as compared to the DTH negative patients. The activation of antigen-specific immune responses by DC vaccine in combination with standard chemotherapy may be associated with a good clinical outcome in advanced pancreatic cancer. We are now planning a pivotal study of the Vaccell in appropriate protocols in Japan.

  2. Precursor Lesions for Sporadic Pancreatic Cancer: PanIN, IPMN, and MCN

    Directory of Open Access Journals (Sweden)

    M. Distler

    2014-01-01

    Full Text Available Pancreatic cancer is still a dismal disease. The high mortality rate is mainly caused by the lack of highly sensitive and specific diagnostic tools, and most of the patients are diagnosed in an advanced and incurable stage. Knowledge about precursor lesions for pancreatic cancer has grown significantly over the last decade, and nowadays we know that mainly three lesions (PanIN, and IPMN, MCN are responsible for the development of pancreatic cancer. The early detection of these lesions is still challenging but provides the chance to cure patients before they might get an invasive pancreatic carcinoma. This paper focuses on PanIN, IPMN, and MCN lesions and reviews the current level of knowledge and clinical measures.

  3. Precursor lesions for sporadic pancreatic cancer: PanIN, IPMN, and MCN.

    Science.gov (United States)

    Distler, M; Aust, D; Weitz, J; Pilarsky, C; Grützmann, Robert

    2014-01-01

    Pancreatic cancer is still a dismal disease. The high mortality rate is mainly caused by the lack of highly sensitive and specific diagnostic tools, and most of the patients are diagnosed in an advanced and incurable stage. Knowledge about precursor lesions for pancreatic cancer has grown significantly over the last decade, and nowadays we know that mainly three lesions (PanIN, and IPMN, MCN) are responsible for the development of pancreatic cancer. The early detection of these lesions is still challenging but provides the chance to cure patients before they might get an invasive pancreatic carcinoma. This paper focuses on PanIN, IPMN, and MCN lesions and reviews the current level of knowledge and clinical measures.

  4. Selection and Outcome of Portal Vein Resection in Pancreatic Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Nakao, Akimasa [Department of Surgery II, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550 (Japan)

    2010-11-24

    Pancreatic cancer has the worst prognosis of all gastrointestinal neoplasms. Five-year survival of pancreatic cancer after pancreatectomy is very low, and surgical resection is the only option to cure this dismal disease. The standard surgical procedure is pancreatoduodenectomy (PD) for pancreatic head cancer. The morbidity and especially the mortality of PD have been greatly reduced. Portal vein resection in pancreatic cancer surgery is one attempt to increase resectability and radicality, and the procedure has become safe to perform. Clinicohistopathological studies have shown that the most important indication for portal vein resection in patients with pancreatic cancer is the ability to obtain cancer-free surgical margins. Otherwise, portal vein resection is contraindicated.

  5. α-Mangostin inhibits hypoxia-driven ROS-induced PSC activation and pancreatic cancer cell invasion.

    Science.gov (United States)

    Lei, Jianjun; Huo, Xiongwei; Duan, Wanxing; Xu, Qinhong; Li, Rong; Ma, Jiguang; Li, Xuqi; Han, Liang; Li, Wei; Sun, Hao; Wu, Erxi; Ma, Qingyong

    2014-05-28

    Recent advances indicating a key role of microenvironment for tumor progression, we investigated the role of PSCs and hypoxia in pancreatic cancer aggressiveness, and examined the potential protective effect of α-mangostin on hypoxia-driven pancreatic cancer progression. Our data indicate that hypoxic PSCs exploit their oxidative stress due to hypoxia to secrete soluble factors favouring pancreatic cancer invasion. α-Mangostin suppresses hypoxia-induced PSC activation and pancreatic cancer cell invasion through the inhibition of HIF-1α stabilization and GLI1 expression. Increased generation of hypoxic ROS is responsible for HIF-1α stabilization and GLI1 upregulation. Therefore, α-mangostin may be beneficial in preventing hypoxia-induced pancreatic cancer progression.

  6. New targeted therapies in pancreatic cancer.

    Science.gov (United States)

    Seicean, Andrada; Petrusel, Livia; Seicean, Radu

    2015-05-28

    Patients with pancreatic cancer have a poor prognosis with a median survival of 4-6 mo and a 5-year survival of less than 5%. Despite therapy with gemcitabine, patient survival does not exceed 6 mo, likely due to natural resistance to gemcitabine. Therefore, it is hoped that more favorable results can be obtained by using guided immunotherapy against molecular targets. This review summarizes the new leading targeted therapies in pancreatic cancers, focusing on passive and specific immunotherapies. Passive immunotherapy may have a role for treatment in combination with radiochemotherapy, which otherwise destroys the immune system along with tumor cells. It includes mainly therapies targeting against kinases, including epidermal growth factor receptor, Ras/Raf/mitogen-activated protein kinase cascade, human epidermal growth factor receptor 2, insulin growth factor-1 receptor, phosphoinositide 3-kinase/Akt/mTOR and hepatocyte growth factor receptor. Therapies against DNA repair genes, histone deacetylases, microRNA, and pancreatic tumor tissue stromal elements (stromal extracellular matric and stromal pathways) are also discussed. Specific immunotherapies, such as vaccines (whole cell recombinant, peptide, and dendritic cell vaccines), adoptive cell therapy and immunotherapy targeting tumor stem cells, have the role of activating antitumor immune responses. In the future, treatments will likely include personalized medicine, tailored for numerous molecular therapeutic targets of multiple pathogenetic pathways.

  7. Selected cytokines in patients with pancreatic cancer: a preliminary report.

    Directory of Open Access Journals (Sweden)

    Wojciech Błogowski

    Full Text Available BACKGROUND/AIMS: Recent experimental studies have suggested that various cytokines may be important players in the development and progression of pancreatic cancer. However, these findings have not yet been verified in a clinical setting. METHODS: In this study, we examined the levels of a broad panel of cytokines, including interleukin (IL-1, IL-6, IL-8, IL-10, IL-12, IL-17, and IL-23, as well as tumor necrosis factor alpha (TNFα and granulocyte-colony stimulating factor (G-CSF in patients with pancreatic adenocarcinoma (n=43, other pancreatic malignancies (neuroendocrine [n=10] and solid pseudopapillary tumors [n=3], and healthy individuals (n=41. RESULTS: We found that there were higher levels of IL-6, IL-8, IL-10 and TNFα in patients with pancreatic cancer compared to healthy controls (for all, at least p<0.03. Cancer patients had lower IL-23 concentrations than healthy individuals and patients diagnosed with other types of malignancies (for both, p=0.002. Levels of IL-6, IL-8, IL-10, and IL-23 were significantly associated with the direct number of circulating bone marrow (BM-derived mesenchymal or very small embryonic/epiblast-like stem cells (SCs in patients with pancreatic cancer. Moreover, our study identified a potential ability of IL-6, IL-8, IL-10, IL-23, and TNFα levels to enable discrimination of pancreatic cancer from other pancreatic tumors and diseases, including acute and chronic pancreatitis and post-pancreatitis cysts (with sensitivity and specificity ranging between 70%-82%. CONCLUSIONS: Our study i supports the significance of selected cytokines in the clinical presentation of pancreatic cancer, ii highlights numerous associations between selected interleukins and intensified BMSCs trafficking in patients with pancreatic cancer, and iii preliminarily characterizes the diagnostic potential of several cytokines as potential novel clinical markers of pancreatic cancer in humans.

  8. Advanced endoscopic ultrasound management techniques for preneoplastic pancreatic cystic lesions

    Science.gov (United States)

    Arshad, Hafiz Muhammad Sharjeel; Bharmal, Sheila; Duman, Deniz Guney; Liangpunsakul, Suthat; Turner, Brian G

    2017-01-01

    Pancreatic cystic lesions can be benign, premalignant or malignant. The recent increase in detection and tremendous clinical variability of pancreatic cysts has presented a significant therapeutic challenge to physicians. Mucinous cystic neoplasms are of particular interest given their known malignant potential. This review article provides a brief but comprehensive review of premalignant pancreatic cystic lesions with advanced endoscopic ultrasound (EUS) management approaches. A comprehensive literature search was performed using PubMed, Cochrane, OVID and EMBASE databases. Preneoplastic pancreatic cystic lesions include mucinous cystadenoma and intraductal papillary mucinous neoplasm. The 2012 International Sendai Guidelines guide physicians in their management of pancreatic cystic lesions. Some of the advanced EUS management techniques include ethanol ablation, chemotherapeutic (paclitaxel) ablation, radiofrequency ablation and cryotherapy. In future, EUS-guided injections of drug-eluting beads and neodymium:yttrium aluminum agent laser ablation is predicted to be an integral part of EUS-guided management techniques. In summary, International Sendai Consensus Guidelines should be used to make a decision regarding management of pancreatic cystic lesions. Advanced EUS techniques are proving extremely beneficial in management, especially in those patients who are at high surgical risk. PMID:27574295

  9. Apoptosis of human pancreatic cancer cells induced by Triptolide

    Institute of Scientific and Technical Information of China (English)

    Guo-Xiong Zhou; Xiao-Ling Ding; Jie-Fei Huang; Hong Zhang; Sheng-Bao Wu; Jian-Ping Cheng; Qun Wei

    2008-01-01

    AIM:To investigate apoptosis in human pancreatic cancer ceils induced by Triptolide (TL),and the relationship between this apoptosis and expression of caspase-3' bcl-2 and bax.METHODS:Human pancreatic cancer cell line SW1990 was cultured in DIEM media for this study.MTT assay was used to determine the cell growth inhibitory rate in vitro.Flow cytometry and TUNEL assay were used to detect the apoptosis of human pancreatic cancer cells before and after TL treatment.RT-PCR was used to detect the expression of apoptosis-associated gene caspase-3' bcl-2 and bax.RESULTS:TL inhibited the growth of human pancreatic cancer cells in a dose-and time-dependent manner.TL induced human pancreatic cancer cells to undergo apoptosis with typically apoptotic characteristics.TUNEL assay showed that after the treatment of human pancreatic cancer cells with 40 ng/mL TL for 12 h and 24 h,the apoptotic rates of human pancreatic cancer cells increased significantly.RT-PCR demonstrated that caspase-3 and bax were significantly up-regulated in SW1990 cells treated with TL while bcl-2 mRNA was not.CONCLUSION:TL is able to induce the apoptosis in human pancreatic cancer cells.This apoptosis may be mediated by up-regulating the expression of apoptosisassociated caspase-3 and bax gene.

  10. Cholecystokinin and pancreatic cancer: the chicken or the egg?

    Science.gov (United States)

    Smith, Jill P; Solomon, Travis E

    2014-01-01

    The gastrointestinal peptide cholecystokinin (CCK) causes the release of pancreatic digestive enzymes and growth of the normal pancreas. Exogenous CCK administration has been used in animal models to study pancreatitis and also as a promoter of carcinogen-induced or Kras-driven pancreatic cancer. Defining CCK receptors in normal human pancreas has been problematic because of its retroperitoneal location, high concentrations of pancreatic proteases, and endogenous RNase. Most studies indicate that the predominant receptor in human pancreas is the CCK-B type, and CCK-A is the predominant form in rodent pancreas. In pancreatic cancer cells and tumors, the role of CCK is better established because receptors are often overexpressed by these cancer cells and stimulation of such receptors promotes growth. Furthermore, in established cancer, endogenous production of CCK and/or gastrin occurs and their actions stimulate the synthesis of more receptors plus growth by an autocrine mechanism. Initially it was thought that the mechanism by which CCK served to potentiate carcinogenesis was by interplay with inflammation in the pancreatic microenvironment. But with the recent findings of CCK receptors on early PanIN (pancreatic intraepithelial neoplasia) lesions and on stellate cells, the question has been raised that perhaps CCK actions are not the result of cancer but an early driving promoter of cancer. This review will summarize what is known regarding CCK, its receptors, and pancreatic cancer, and also what is unknown and requires further investigation to determine which comes first, the chicken or the egg, "CCK or the cancer."

  11. Radical resection of pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    Alexander Koliopanos; C Avgerinos; Athanasios Farfaras; C Manes; Christos Dervenis

    2008-01-01

    BACKGROUND:Pancreatic adenocarcinoma (PCa) is a disease with dismal prognosis, and the only possibility of cure, albeit small, is based on the combination of complete resection with negative histopathological margins (R0 resection) with adjuvant treatment. Therefore, a lot of effort has been made during the last decade to assess the role of extensive surgery in both local recurrence and survival of patients with PCa. DATA SOURCES:Medline search and manual cross-referencing were utilized to identify published evidence-based data for PCa surgery between 1973 and 2006, with emphasis to feasibility, efifcacy, long-term survival, disease free survival, recurrence rates, pain relief and quality of life. RESULTS: Extended surgery is safe and feasible in high volume surgical centers with comparable short-term results. Organ preserving surgery is a main goal because of quality of life reasons and is performed whenever possible from the tumor extent. Concerning long-term survival major vein resection does not adversely affect outcome. To date, there are no changes in long-term survival attributed to the extended lymph node dissection. However, there is a beneift in locoregional control with fewer local recurrences and extended lymphadenectomy allows better staging for the disease. CONCLUSIONS:Extended PCa surgery is safe and feasible despite the inconclusive results in patient's survival beneift. In the future, appropriately powered randomized trials of standard vs. extended resections may show improved outcomes for PCa patients.

  12. Limitation of CT in diagnosis of pancreatic cancer

    Energy Technology Data Exchange (ETDEWEB)

    Honda, Hiroshi (Kyushu Univ., Fukuoka (Japan). Faculty of Medicine); Kusumoto, Shizuo; Nishikawa, Kiyoshi (and others)

    The differentiation of pancreatic abnormalities remains a problem. We analyzed the sensitivity and specificity of computed tomography (CT) in the diagnosis of pancreatic disease, using six radiologists who had less than six months' training in CT (resident level: inexperienced) and six who had more than 12 months' training (staff level: experienced) in order to clarify the difficulty with CT in the qualitative diagnosis of pancreatic cancer. We reviewed retrospectively 100 cases: 28 cases of pancreatic cancer, 15 of chronic pancreatitis, three of acute pancreatitis, 12 of neoplastic disease that involved the pancreas, and 42 normal subjects. The average sensitivity and specificity of CT in the diagnosis of pancreatic disease were 81.3% and 84.4%, respectively, for the experienced radiologists and 64.0% and 82.1%, respectively, for the inexperienced radiologists. The averages for pancreatic cancer were 65.3% and 87.8% for the experienced radiologists and 60.7% and 87.3% for the inexperienced radiologists. We conclude that the ability to detect pancreatic abnormalities improves with training and experience, but diagnosis of pancreatic cancer does not improve after a certain level of expertise. (author).

  13. Pancreatic Resections for Advanced M1-Pancreatic Carcinoma: The Value of Synchronous Metastasectomy

    Directory of Open Access Journals (Sweden)

    S. K. Seelig

    2010-01-01

    Materials and Methods. From January 1, 2004 to December, 2007 a total of 20 patients with pancreatic malignancies were retrospectively evaluated who underwent pancreatic surgery with synchronous resection of hepatic, adjacent organ, or peritoneal metastases for proven UICC stage IV periampullary cancer of the pancreas. Perioperative as well as clinicopathological parameters were evaluated. Results. There were 20 patients (9 men, 11 women; mean age 58 years identified. The primary tumor was located in the pancreatic head (n=9, 45%, in pancreatic tail (n=9, 45%, and in the papilla Vateri (n=2, 10%. Metastases were located in the liver (n=14, 70%, peritoneum (n=5, 25%, and omentum majus (n=2, 10%. Lymphnode metastases were present in 16 patients (80%. All patients received resection of their tumors together with metastasectomy. Pylorus preserving duodenopancreatectomy was performed in 8 patients, distal pancreatectomy in 8, duodenopancreatectomy in 2, and total pancreatectomy in 2. Morbidity was 45% and there was no perioperative mortality. Median postoperative survival was 10.7 months (2.6–37.7 months which was not significantly different from a matched-pair group of patients who underwent pancreatic resection for UICC adenocarcinoma of the pancreas (median survival 15.6 months; P=.1. Conclusion. Pancreatic resection for M1 periampullary cancer of the pancreas can be performed safely in well-selected patients. However, indication for surgery has to be made on an individual basis.

  14. Anti-angiogenic activity of VXM01, an oral T-cell vaccine against VEGF receptor 2, in patients with advanced pancreatic cancer: A randomized, placebo-controlled, phase 1 trial.

    Science.gov (United States)

    Schmitz-Winnenthal, Friedrich H; Hohmann, Nicolas; Niethammer, Andreas G; Friedrich, Tobias; Lubenau, Heinz; Springer, Marco; Breiner, Klaus M; Mikus, Gerd; Weitz, Jürgen; Ulrich, Alexis; Buechler, Markus W; Pianka, Frank; Klaiber, Ulla; Diener, Markus; Leowardi, Christine; Schimmack, Simon; Sisic, Leila; Keller, Anne-Valerie; Koc, Ruhan; Springfeld, Christoph; Knebel, Philipp; Schmidt, Thomas; Ge, Yingzi; Bucur, Mariana; Stamova, Slava; Podola, Lilli; Haefeli, Walter E; Grenacher, Lars; Beckhove, Philipp

    2015-04-01

    VEGFR-2 is expressed on tumor vasculature and a target for anti-angiogenic intervention. VXM01 is a first in kind orally applied tumor vaccine based on live, attenuated Salmonella bacteria carrying an expression plasmid, encoding VEGFR-2. We here studied the safety, tolerability, T effector (Teff), T regulatory (Treg) and humoral responses to VEGFR2 and anti-angiogenic effects in advanced pancreatic cancer patients in a randomized, dose escalation phase I clinical trial. Results of the first 3 mo observation period are reported. Locally advanced or metastatic, pancreatic cancer patients were enrolled. In five escalating dose groups, 30 patients received VXM01 and 15 placebo on days 1, 3, 5, and 7. Treatment was well tolerated at all dose levels. No dose-limiting toxicities were observed. Salmonella excretion and salmonella-specific humoral immune responses occurred in the two highest dose groups. VEGFR2 specific Teff, but not Treg responses were overall increased in vaccinated patients. We furthermore observed a significant reduction of tumor perfusion after 38 d in vaccinated patients together with increased levels of serum biomarkers indicative of anti-angiogenic activity, VEGF-A, and collagen IV. Vaccine specific Teff responses significantly correlated with reductions of tumor perfusion and high levels of preexisting VEGFR2-specific Teff while those showing no antiangiogenic activity had low levels of preexisting VEGFR2 specific Teff, showed a transient early increase of VEGFR2-specific Treg and reduced levels of VEGFR2-specific Teff at later time points - pointing to the possibility that early anti-angiogenic activity might be based at least in part on specific reactivation of preexisting memory T cells.

  15. c-Met in pancreatic cancer stem cells: Therapeutic implications

    Institute of Scientific and Technical Information of China (English)

    Marta Herreros-Villanueva; Aizpea Zubia-Olascoaga; Luis Bujanda

    2012-01-01

    Pancreatic cancer is the deadliest solid cancer and currently the fourth most frequent cause of cancer-related deaths.Emerging evidence suggests that cancer stem cells (CSCs) play a crucial role in the development and progression of this disease.The identification of CSC markers could lead to the development of new therapeutic targets.In this study,the authors explore the functional role of c-Met in pancreatic CSCs,by analyzing self-renewal with sphere assays and tumorigenicity capacity in NOD SCID mice.They concluded that c-Met is a novel marker for identifying pancreatic CSCs and c-Methigh in a higher tumorigenic cancer cell population.Inhibition of c-Met with XL184 blocks self-renewal capacity in pancreatic CSCs.In pancreatic tumors established in NOD SCID mice,c-Met inhibition slowed tumor growth and reduced the population of CSCs,along with preventing the development of metastases.

  16. Advances in Cancer Therapy

    OpenAIRE

    Jordan BF, Sonveaux P

    2011-01-01

    The book "Advances in Cancer Therapy" is a new addition to the Intech collection of books and aims at providing scientists and clinicians with a comprehensive overview of the state of current knowledge and latest research findings in the area of cancer therapy. For this purpose research articles, clinical investigations and review papers that are thought to improve the readers' understanding of cancer therapy developments and/or to keep them up to date with the most recent advances in this fi...

  17. [Tumor markers in the diagnosis of pancreatic cancer].

    Science.gov (United States)

    Cappelli, G; Paladini, S; D'Agata, A

    1999-01-01

    The difficulty in an early diagnosis of pancreatic cancer is in the absence of early symptoms due to lower limit of detection of the actual imaging techniques. Clinical symptoms like weight loss, abdominal pain and jaundice indicate an advanced cancer stage. Today 50% of pancreatic tumors are diagnosed in advanced metastatic stage and only 20-30% show resectable cancer. Ultrasound and determination of a mucine like antigen as CA 19-9, CA 50 and CA 195 seem to allow an earlier diagnosis with a higher rate of resective surgery and a prolonged survival for these patients. The mucines are high molecular weight glycoproteins consistent of a backbone protein to which oligosaccarides are attached. The linkage of carbohydrate to the peptide is termed O-glycosidic and involves the hydroxylic groups of serine or threonine with N-acetylglucosamine. Only the backbone proteins are genetically determined (genes MUC). The gangliosides are the same or derivative of Lewis antigen. CA 19-9, CA 50 and CA 195 are assays directed to different epitopes probably present on the same mucinous antigen. These epitopes are not present in different mucines as CA 15-3, CA 125 and TAG 72. Recently other two mucines are emploied CA 242 and CAM 17.1 but they are not better than CA 19-9. The use of a "triplet" of tumor markers as CA 19-9, CA 125 and CEA is the best diagnostic tool for cancer of pancreas in an "integrated" use with ultrasonographic evaluation of the lesion. CA 19-9 permits differential diagnosis from neuroendocrine tumor or pancreatitis, the values of CA 125 and CEA are useful in the evaluation of the stage, resectability and prognosis of pancreatic cancer. The recent use of CA19-9 for the evaluation of radiochemotherapy in preoperative management of the patient is a mode of a well known application of tumor markers in a kinetic evaluation of the tumor for the radicality of therapy, follow-up, recurrence and the effectiveness of the palliative therapy.

  18. Nek2 siRNA therapy using a portal venous port-catheter system for liver metastasis in pancreatic cancer.

    Science.gov (United States)

    Kokuryo, Toshio; Hibino, Shigeru; Suzuki, Kazushi; Watanabe, Katsutaka; Yokoyama, Yukihiro; Nagino, Masato; Senga, Takeshi; Hamaguchi, Michinari

    2016-09-01

    Nek2 (NIMA-related kinase 2) is a serine-threonine kinase and human homolog of the mitotic regulator NIMA of Aspergillus nidulan. We reported the efficiency of Nek2 siRNA in several cancer xenograft models using cholangiocarcinoma, breast cancer and colorectal cancer. Pancreatic cancer is difficult to treat due to its rapid progression and resistance to chemotherapy. Novel treatments are urgently required to improve survival in pancreatic cancer, and siRNA are a promising therapeutic option. However, finding an in vivo drug delivery system of siRNA remains a major problem for clinical application. In this study, the overexpression of Nek2 was identified in pancreatic cancer cell lines. Nek2 siRNA inhibited tumor growth in a subcutaneous xenograft mouse model of pancreatic cancer, prolonged the survival time in an intraperitoneal xenograft mouse model and efficiently prevented the progression of liver metastasis using a portal venous port-catheter system. Taken together, Nek2 is an effective therapeutic target in pancreatic cancer. An adequate delivery system is considered important in treating advanced pancreatic cancer, such as peritoneal dissemination and liver metastasis. Further investigations are required on the safety and side effects of the portal venous port-catheter system. We hope that Nek2 siRNA will be a novel therapeutic strategy for pancreatic cancer with liver metastasis and peritoneal dissemination.

  19. A Case of Pancreatic Cancer in the Setting of Autoimmune Pancreatitis with Nondiagnostic Serum Markers

    Directory of Open Access Journals (Sweden)

    Manju D. Chandrasegaram

    2013-01-01

    Full Text Available Background. Autoimmune pancreatitis (AIP often mimics pancreatic cancer. The diagnosis of both conditions is difficult preoperatively let alone when they coexist. Several reports have been published describing pancreatic cancer in the setting of AIP. Case Report. The case of a 53-year-old man who presented with abdominal pain, jaundice, and radiological features of autoimmune pancreatitis, with a “sausage-shaped” pancreas and bulky pancreatic head with portal vein impingement, is presented. He had a normal serum IgG4 and only mildly elevated Ca-19.9. Initial endoscopic ultrasound-(EUS- guided fine-needle aspiration (FNA of the pancreas revealed an inflammatory sclerosing process only. A repeat EUS guided biopsy following biliary decompression demonstrated both malignancy and features of autoimmune pancreatitis. At laparotomy, a uniformly hard, bulky pancreas was found with no sonographically definable mass. A total pancreatectomy with portal vein resection and reconstruction was performed. Histology revealed adenosquamous carcinoma of the pancreatic head and autoimmune pancreatitis and squamous metaplasia in the remaining pancreas. Conclusion. This case highlights the diagnostic and management difficulties in a patient with pancreatic cancer in the setting of serum IgG4-negative, Type 2 AIP.

  20. Spontaneous regression of pancreatic cancer: Real or a misdiagnosis?

    Institute of Scientific and Technical Information of China (English)

    Marta Herreros-Villanueva; Elizabeth Hijona; Angel Cosme; Luis Bujanda

    2012-01-01

    Spontaneous tumor regression has been subject of numerous studies and speculations for many years.This phenomenon is exceptional,but well reported,in some types of tumors,but not in pancreatic cancer.Pancreatic cancer has the worst five-year survival rate of any cancer.Despite numerous molecular studies and clinical approaches,using several mouse models,this cancer responds poorly to the existing chemotherapeutic agents and progress on treatment remains elusive.Although pancreatic cancer tumors seldom undergo spontaneous regression,and some authors take that with skepticism,there are some cases reported in the literature.However,the variability in the description of the reports and technical details could make this process susceptible to misdiagnosis.Distinguishing between different types of pancreatic carcinoma should be taken with caution as they have wide differences in malignant potential.Diseases such as pancreatic benign tumors,insulinomas,or autoimmune pancreatitis could be responsible for this misdiagnosis as a pancreatic cancer.Here we review different cases reported,their clinical characteristics,and possible mechanisms leading to spontaneous regression of pancreatic cancer.We also discuss the possibilities of misdiagnosis.

  1. Tumor markers in pancreatic cancer: a European Group on Tumor Markers (EGTM) status report.

    LENUS (Irish Health Repository)

    Duffy, M J

    2012-02-01

    Pancreatic ductal adenocarcinoma is one of the most difficult malignancies to diagnose and treat. The aim of this article is to review how tumor markers can aid the diagnosis and management of patients with this malignancy. The most widely used and best validated marker for pancreatic cancer is CA 19-9. Inadequate sensitivity and specificity limit the use of CA 19-9 in the early diagnosis of pancreatic cancer. In non-jaundiced patients, however, CA 19-9 may complement other diagnostic procedures. In patients with resectable pancreatic cancer, presurgical and postresection CA 19-9 levels correlate with overall survival. In advanced disease, elevated pretreatment levels of CA 19-9 are associated with adverse patient outcome and thus may be combined with other factors for risk stratification. Most, but not all, reports indicate that serial levels of CA 19-9 correlate with response to systemic therapy. Use of CA 19-9 kinetics in conjunction with imaging is therefore recommended in monitoring therapy. Although several potential serum and tissue markers for pancreatic cancer are currently undergoing evaluation, none are sufficiently validated for routine clinical use. CA 19-9 thus remains the serum pancreatic cancer marker against which new markers for this malignancy should be judged.

  2. Salivary MicroRNA in Pancreatic Cancer Patients.

    Directory of Open Access Journals (Sweden)

    Marine Humeau

    Full Text Available Pancreatic cancer is the fourth leading cause of cancer death in Western countries, with the lowest 1-year survival rate among commonly diagnosed cancers. Reliable biomarkers for pancreatic cancer diagnosis are lacking and are urgently needed to allow for curative surgery. As microRNA (miRNA recently emerged as candidate biomarkers for this disease, we explored in the present pilot study the differences in salivary microRNA profiles between patients with pancreatic tumors that are not eligible for surgery, precancerous lesions, inflammatory disease or cancer-free patients as a potential early diagnostic tool.Whole saliva samples from patients with pancreatic cancer (n = 7, pancreatitis (n = 4, IPMN (n = 2, or healthy controls (n = 4 were obtained during endoscopic examination. After total RNA isolation, expression of 94 candidate miRNAs was screened by q(RTPCR using Biomark Fluidgm. Human-derived pancreatic cancer cells were xenografted in athymic mice as an experimental model of pancreatic cancer.We identified hsa-miR-21, hsa-miR-23a, hsa-miR-23b and miR-29c as being significantly upregulated in saliva of pancreatic cancer patients compared to control, showing sensitivities of 71.4%, 85.7%, 85,7% and 57%, respectively and excellent specificity (100%. Interestingly, hsa-miR-23a and hsa-miR23b are overexpressed in the saliva of patients with pancreatic cancer precursor lesions. We found that hsa-miR-210 and let-7c are overexpressed in the saliva of patients with pancreatitis as compared to the control group, with sensitivity of 100% and 75%, and specificity of 100% and 80%, respectively. Last hsa-miR-216 was upregulated in cancer patients as compared to patients diagnosed with pancreatitis, with sensitivity of 50% and specificity of 100%. In experimental models of PDAC, salivary microRNA detection precedes systemic detection of cancer cells markers.Our novel findings indicate that salivary miRNA are discriminatory in pancreatic cancer patients

  3. Diagnosis of pancreatic cancer by cytology and telomerase activity in exfoliated cells obtained by pancreatic duct brushing during endoscopy

    Institute of Scientific and Technical Information of China (English)

    Guo-Xiong Zhou; Jie-Fei Huang; Hong Zhang; Jian-Ping Chen

    2007-01-01

    BACKGROUND:Telomerase activity is reported to be speciifc and frequent in human pancreatic cancer. We conducted this study to assess the usefulness of monitoring telomerase activity in exfoliated cells obtained by pancreatic duct brushing during endoscopic retrograde cholangiopancreatography (ERCP) for the diagnosis of pancreatic cancer. METHODS:Exfoliated cells obtained by pancreatic duct brushing during ERCP from 21 patients (18 with pancreatic cancer, 3 with chronic pancreatitis) were examined. Telomerase activity was detected by polymerase chain reaction and telomeric repeat ampliifcation protocol assay (PCR-TRAP-ELISA). RESULTS:D450 values of telomerase activity were 0.446± 0.2700 in pancreatic cancer and 0.041±0.0111 in chronic pancreatitis. 77.8% (14/18) of patients with pancreatic cancer had cells with telomerase activity. None of the samples from patients with chronic pancreatitis showed telomerase activity, when the cutoff value of telomerase activity was set at 2.0. Cytological examination showed cancer cells in 66.7%(12/18) of the patients. CONCLUSIONS:Telomerase activity may be an early malignant event in pancreatic cancer development. Cytology and telomerase activity in cells obtained by pancreatic duct brushing may complement each other for the diagnosis of pancreatic cancer.

  4. [Surgery for pancreatic cancer: Evidence-based surgical strategies].

    Science.gov (United States)

    Sánchez Cabús, Santiago; Fernández-Cruz, Laureano

    2015-01-01

    Pancreatic cancer surgery represents a challenge for surgeons due to its technical complexity, the potential complications that may appear, and ultimately because of its poor survival. The aim of this article is to summarize the scientific evidence regarding the surgical treatment of pancreatic cancer in order to help surgeons in the decision making process in the management of these patients .Here we will review such fundamental issues as the need for a biopsy before surgery, the type of pancreatic anastomosis leading to better results, and the need for placement of drains after pancreatic surgery will be discussed.

  5. Improving Goals of Care Discussion in Advanced Cancer Patients

    Science.gov (United States)

    2016-12-20

    Primary Stage IV Hepatobiliary; Esophageal; Colorectal Cancer; Glioblastoma; Cancer of Stomach; Cancer of Pancreas; Melanoma; Head or Neck Cancer; Stage III; Stage IV; Lung Cancers; Pancreatic Cancers

  6. Is metastatic pancreatic cancer an untargetable malignancy?

    Institute of Scientific and Technical Information of China (English)

    Hampig Raphael Kourie; Joseph Gharios; Fadi Elkarak; Joelle Antoun; Marwan Ghosn

    2016-01-01

    Metastatic pancreatic cancer(MPC) is one of the most aggressive malignancies, known to be chemo-resistant and have been recently considered resistant to some targeted therapies(TT). Erlotinib combined to gemcitabine is the only targeted therapy that showed an overall survival benefit in MPC. New targets and therapeutic approaches, based on new-TT, are actually being evaluated in MPC going from immunotherapy, epigenetics, tumor suppressor gene and oncogenes to stromal matrix regulators. We aim in this paper to present the major causes rendering MPC an untargetable malignancy and to focus on the new therapeutic modalities based on TT in MPC.

  7. Vitamin D metabolic pathway genes and pancreatic cancer risk.

    Directory of Open Access Journals (Sweden)

    Hannah Arem

    Full Text Available Evidence on the association between vitamin D status and pancreatic cancer risk is inconsistent. This inconsistency may be partially attributable to variation in vitamin D regulating genes. We selected 11 vitamin D-related genes (GC, DHCR7, CYP2R1, VDR, CYP27B1, CYP24A1, CYP27A1, RXRA, CRP2, CASR and CUBN totaling 213 single nucleotide polymorphisms (SNPs, and examined associations with pancreatic adenocarcinoma. Our study included 3,583 pancreatic cancer cases and 7,053 controls from the genome-wide association studies of pancreatic cancer PanScans-I-III. We used the Adaptive Joint Test and the Adaptive Rank Truncated Product statistic for pathway and gene analyses, and unconditional logistic regression for SNP analyses, adjusting for age, sex, study and population stratification. We examined effect modification by circulating vitamin D concentration (≤50, >50 nmol/L for the most significant SNPs using a subset of cohort cases (n = 713 and controls (n = 878. The vitamin D metabolic pathway was not associated with pancreatic cancer risk (p = 0.830. Of the individual genes, none were associated with pancreatic cancer risk at a significance level of p<0.05. SNPs near the VDR (rs2239186, LRP2 (rs4668123, CYP24A1 (rs2762932, GC (rs2282679, and CUBN (rs1810205 genes were the top SNPs associated with pancreatic cancer (p-values 0.008-0.037, but none were statistically significant after adjusting for multiple comparisons. Associations between these SNPs and pancreatic cancer were not modified by circulating concentrations of vitamin D. These findings do not support an association between vitamin D-related genes and pancreatic cancer risk. Future research should explore other pathways through which vitamin D status might be associated with pancreatic cancer risk.

  8. Review of screening for pancreatic cancer in high risk individuals

    Institute of Scientific and Technical Information of China (English)

    Alina Stoita; Ian D Penman; David B Williams

    2011-01-01

    Pancreatic cancer is difficult to diagnose at an early stage and is associated with a very poor survival. Ten percent of pancreatic cancers result from genetic susceptibility and/or familial aggregation. Individuals from families with multiple affected first-degree relatives and those with a known cancer-causing genetic mutation have been shown to be at much higher risk of developing pancreatic cancer. Recent efforts have focused on detecting disease at an earlier stage to improve survival in these high-risk groups. This article reviews high-risk groups, screening methods, and current screening programs and their results.

  9. Review of screening for pancreatic cancer in high risk individuals.

    Science.gov (United States)

    Stoita, Alina; Penman, Ian D; Williams, David B

    2011-05-21

    Pancreatic cancer is difficult to diagnose at an early stage and is associated with a very poor survival. Ten percent of pancreatic cancers result from genetic susceptibility and/or familial aggregation. Individuals from families with multiple affected first-degree relatives and those with a known cancer-causing genetic mutation have been shown to be at much higher risk of developing pancreatic cancer. Recent efforts have focused on detecting disease at an earlier stage to improve survival in these high-risk groups. This article reviews high-risk groups, screening methods, and current screening programs and their results.

  10. New challenges in perioperative management of pancreatic cancer.

    Science.gov (United States)

    Puleo, Francesco; Maréchal, Raphaël; Demetter, Pieter; Bali, Maria-Antonietta; Calomme, Annabelle; Closset, Jean; Bachet, Jean-Baptiste; Deviere, Jacques; Van Laethem, Jean-Luc

    2015-02-28

    Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer-related death in the industrialized world. Despite progress in the understanding of the molecular and genetic basis of this disease, the 5-year survival rate has remained low and usually does not exceed 5%. Only 20%-25% of patients present with potentially resectable disease and surgery represents the only chance for a cure. After decades of gemcitabine hegemony and limited therapeutic options, more active chemotherapies are emerging in advanced PDAC, like 5-Fluorouracil, folinic acid, irinotecan and oxaliplatin and nab-paclitaxel plus gemcitabine, that have profoundly impacted therapeutic possibilities. PDAC is considered a systemic disease because of the high rate of relapse after curative surgery in patients with resectable disease at diagnosis. Neoadjuvant strategies in resectable, borderline resectable, or locally advanced pancreatic cancer may improve outcomes. Incorporation of tissue biomarker testing and imaging techniques into preoperative strategies should allow clinicians to identify patients who may ultimately achieve curative benefit from surgery. This review summarizes current knowledge of adjuvant and neoadjuvant treatment for PDAC and discusses the rationale for moving from adjuvant to preoperative and perioperative therapeutic strategies in the current era of more active chemotherapies and personalized medicine. We also discuss the integration of good specimen collection, tissue biomarkers, and imaging tools into newly designed preoperative and perioperative strategies.

  11. 3'-Deoxy-3'-{sup 18}F-fluorothymidine positron emission tomography as an early predictor of disease progression in patients with advanced and metastatic pancreatic cancer

    Energy Technology Data Exchange (ETDEWEB)

    Challapalli, Amarnath; Barwick, Tara; Merchant, Shairoz [Imperial College London (ICL), Department of Surgery and Cancer, London (United Kingdom); Pearson, Rachel A.; Howell, Elizabeth C.; Maxwell, Ross J. [Newcastle University, Northern Institute for Cancer Research, Newcastle (United Kingdom); Mauri, Francesco [Imperial College Healthcare NHS Trust, Department of Pathology, London (United Kingdom); Sumpter, Katherine [Northern Centre for Cancer Care, Newcastle Upon Tyne Hospitals NHS Foundation Trust, London (United Kingdom); Aboagye, Eric O. [Imperial College London (ICL), Department of Surgery and Cancer, London (United Kingdom); ICL, Hammersmith Hospital, Department of Surgery and Cancer, London (United Kingdom); Sharma, Rohini [ICL, Department of Investigative Medicine, London (United Kingdom)

    2015-05-01

    3'-Deoxy-3'-{sup 18}F-fluorothymidine (FLT) positron emission tomography (PET) has limited utility in abdominal imaging due to high physiological hepatic uptake of tracer. We evaluated FLT PET/CT combined with a temporal-intensity information-based voxel-clustering approach termed kinetic spatial filtering (FLT PET/CT{sub KSF}) for early prediction of response and survival outcomes in locally advanced and metastatic pancreatic cancer patients receiving gemcitabine-based chemotherapy. Dynamic FLT PET/CT data were collected before and 3 weeks after the first cycle of chemotherapy. Changes in tumour FLT PET/CT variables were determined. The primary end point was RECIST 1.1 response on contrast-enhanced CT after 3 months of therapy. Twenty patients were included. Visual distinction between tumours and normal pancreas was seen in FLT PET{sub KSF} images. All target lesions (>2 cm), including all primary pancreatic tumours, were visualised. Of the 11 liver metastases, 3 (<2 cm) were not visible after kinetic filtering. Of the 20 patients, 7 progressed (35 %). Maximum standardised uptake value at 60 min post-injection (SUV{sub 60,max}) significantly increased in patients with disease progression (p = 0.04). Receiver-operating characteristic curve analysis indicated that a threshold of SUV{sub 60,max} increase of ≥ 12 % resulted in sensitivity, specificity and positive predictive value (PPV) of 71, 100 and 100 %, respectively [area under the curve (AUC) 0.90, p = 0.0001], to predict patients with disease progression. Changes in SUV{sub 60,max} were not predictive of survival. FLT PET/CT detected changes in proliferation, with early increase in SUV{sub 60,max} predicting progressive disease with a high specificity and PPV. Therefore, FLT PET/CT could be used as an early response biomarker for gemcitabine-based chemotherapy, to select a poor prognostic group who may benefit from novel therapeutic agents in advanced and metastatic pancreatic cancer. (orig.)

  12. Epigenetics and pancreatic cancer: pathophysiology and novel treatment aspects.

    Science.gov (United States)

    Neureiter, Daniel; Jäger, Tarkan; Ocker, Matthias; Kiesslich, Tobias

    2014-06-28

    An improvement in pancreatic cancer treatment represents an urgent medical goal. Late diagnosis and high intrinsic resistance to conventional chemotherapy has led to a dismal overall prognosis that has remained unchanged during the past decades. Increasing knowledge about the molecular pathogenesis of the disease has shown that genetic alterations, such as mutations of K-ras, and especially epigenetic dysregulation of tumor-associated genes, such as silencing of the tumor suppressor p16(ink4a), are hallmarks of pancreatic cancer. Here, we describe genes that are commonly affected by epigenetic dysregulation in pancreatic cancer via DNA methylation, histone acetylation or miRNA (microRNA) expression, and review the implications on pancreatic cancer biology such as epithelial-mesenchymal transition, morphological pattern formation, or cancer stem cell regulation during carcinogenesis from PanIN (pancreatic intraepithelial lesions) to invasive cancer and resistance development. Epigenetic drugs, such as DNA methyltransferases or histone deactylase inhibitors, have shown promising preclinical results in pancreatic cancer and are currently in early phases of clinical development. Combinations of epigenetic drugs with established cytotoxic drugs or targeted therapies are promising approaches to improve the poor response and survival rate of pancreatic cancer patients.

  13. Clinical significance of plasma metastin level in pancreatic cancer patients.

    Science.gov (United States)

    Katagiri, Fumihiko; Nagai, Kazuyuki; Kida, Atsushi; Tomita, Kenji; Oishi, Shinya; Takeyama, Masaharu; Doi, Ryuichiro; Fujii, Nobutaka

    2009-03-01

    Metastin, which is a 54-residue peptide coded by KiSS-1 gene, is an endogenous ligand to a G-protein-coupled receptor GPR54. Metastin suppresses a malignant tumor to metastasize and regulates secretion of gonadotropine releasing hormone. Physiological action of metastin has been focused on in oncology. It is reported that less KiSS-1 gene and more hOT7T175 gene which codes GPR54 are expressed in pancreatic cancers than in normal pancreatic tissues; however, there is no study that investigates the relationship between clinicopathological characteristics and plasma metastin concentration in pancreatic cancer patients. The purpose of this study was to investigate the relationship between plasma metastin-like immunoreactive substance (LI) levels and clinical characteristics in pancreatic cancer patients. Thirty-three patients with pathologically confirmed pancreatic cancer before or just after treatments and 24 healthy volunteers were included in the study. Patients were grouped according to the International Union Against Cancer TNM classification. Plasma metastin-LI was measured by enzyme immunoassay. The plasma metastin-LI levels of cancer patients were significantly higher when compared with healthy volunteers. Significant relationship was not found between the plasma metastin-LI levels and the clinicopathological factors such as tumor size, invasion, lymph node metastasis and distant metastasis. The plasma metastin levels may be a significant biomarker to predict the presence of pancreatic cancer and could be used in pancreatic cancer screening.

  14. Should ageism be a stratification factor in patients with pancreatic cancer?

    Science.gov (United States)

    El-Jurdi, Najla H; Saif, Muhammad Wasif

    2014-03-10

    With ageism being a trend worldwide, and age being a known risk factor for pancreatic cancer, the optimal management of pancreatic cancer patients with advance age is becoming more and more of a pertinent discussion amongst GI oncologists, surgical oncologists and radiation oncologists that is being increasingly addressed in studies nowadays. In an attempt to answer the question of whether age should be a cultural bias in decision making in pancreatic cancer patients, we will review Abstracts #287, #310 and #332 that were presented in the 2014 ASCO Gastrointestinal Cancers Symposium. These abstracts explore whether neoadjuvant therapy should be offered to patients older than 75 years to increase the chances of bridging to surgical resectability (Abstract #287), if patients older than age 70 years would benefit from chemotherapy similar to younger patients (Abstract #310), also whether adjuvant radiation therapy and number of lymph nodes resected in patients older than 70 years correlates with overall survival (Abstract #332).

  15. Hereditary Pancreatitis

    Science.gov (United States)

    ... alcohol is a known risk factor for both acute and chronic pancreatitis. Therefore it is recommended that all HP patients ... Pancreatitis Patient Info Animated Pancreas Patient Pancreatic Cancer Chronic Pancreatitis Acute Pancreatitis Research Research Grant Application Research History Grant ...

  16. Palliative Interventional and Surgical Therapy for Unresectable Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Helmut Friess

    2011-02-01

    Full Text Available Palliative treatment concepts are considered in patients with non-curatively resectable and/or metastasized pancreatic cancer. However, patients without metastases, but presented with marginally resectable or locally non-resectable tumors should not be treated by a palliative therapeutic approach. These patients should be enrolled in neoadjuvant radiochemotherapy trials because a potentially curative resection can be achieved in approximately one-third of them after finishing treatment and restaging. Within the scope of best possible palliative care, resection of the primary cancer together with excision of metastases represents a therapeutic option to be contemplated in selected cases. Comprehensive palliative therapy is based on treatment of bile duct or duodenal obstruction for certain locally unresectable or metastasized advanced pancreatic cancer. However, endoscopic or percutaneous stenting procedures and surgical bypass provide safe and highly effective therapeutic alternatives. In case of operative drainage of the biliary tract (biliodigestive anastomosis, the prophylactic creation of a gastro-intestinal bypass (double bypass is recommended. The decision to perform a surgical versus an endoscopic procedure for palliation depends to a great extent on the tumor stage and the estimated prognosis, and should be determined by an interdisciplinary team for each patient individually.

  17. Palliative Interventional and Surgical Therapy for Unresectable Pancreatic Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Assfalg, Volker; Hüser, Norbert; Michalski, Christoph; Gillen, Sonja; Kleeff, Jorg; Friess, Helmut, E-mail: friess@chir.med.tu-muenchen.de [Department of Surgery, Klinikum rechts der Isar, Technische Universität München, Ismaningerstr. 22, D-81675 Munich (Germany)

    2011-02-14

    Palliative treatment concepts are considered in patients with non-curatively resectable and/or metastasized pancreatic cancer. However, patients without metastases, but presented with marginally resectable or locally non-resectable tumors should not be treated by a palliative therapeutic approach. These patients should be enrolled in neoadjuvant radiochemotherapy trials because a potentially curative resection can be achieved in approximately one-third of them after finishing treatment and restaging. Within the scope of best possible palliative care, resection of the primary cancer together with excision of metastases represents a therapeutic option to be contemplated in selected cases. Comprehensive palliative therapy is based on treatment of bile duct or duodenal obstruction for certain locally unresectable or metastasized advanced pancreatic cancer. However, endoscopic or percutaneous stenting procedures and surgical bypass provide safe and highly effective therapeutic alternatives. In case of operative drainage of the biliary tract (biliodigestive anastomosis), the prophylactic creation of a gastro-intestinal bypass (double bypass) is recommended. The decision to perform a surgical versus an endoscopic procedure for palliation depends to a great extent on the tumor stage and the estimated prognosis, and should be determined by an interdisciplinary team for each patient individually.

  18. Occupational exposures and risk of pancreatic cancer.

    Science.gov (United States)

    Santibañez, Miguel; Vioque, Jesús; Alguacil, Juan; de la Hera, Manuela García; Moreno-Osset, Eduardo; Carrato, Alfredo; Porta, Miquel; Kauppinen, Timo

    2010-10-01

    The objective was to analyze the relationship between occupation (and specific occupational exposures) and risk of exocrine pancreatic cancer (EPC). We conducted a multicenter hospital-based case-control study in Eastern Spain. We included 161 incident cases of EPC (59.6% men, 94 with histological confirmation, of whom 80% had ductal adenocarcinoma). Cases were frequency-matched with 455 controls by sex, age and province of residence. Information was elicited using structured questionnaires. Occupations were coded according to the Spanish version of the International Standard Classification of Occupations 1988. Occupational exposure to a selection of carcinogenic substances was assessed with the Finnish Job-Exposure Matrix (FINJEM). Odds ratios (OR) and 95% confidence intervals (CI) were estimated by multiple logistic regression, adjusting for sex, age, province, education, alcohol and smoking. A higher risk of EPC was associated with having worked as 'Miners, shotfirers, stone cutters and carvers', 'Machinery mechanics and fitters', 'Building trades workers' and 'Motor vehicle drivers' in men, 'Office Clerks' in women, and 'Waiters' in both sexes. Cases with ductal adenocarcinomas were more likely to have been exposed to chlorinated hydrocarbon solvents (OR = 4.1, 95% CI: 1.1-15.2, p-trend = 0.04). We also observed significant associations with exposure to 'synthetic polymer dust exposure' and 'ionizing radiation'. Suggestive increases in risk were observed for 'pesticides', 'diesel and gasoline engine exhaust', and 'hydrocarbon solvents'. Results support the hypothesis that occupational exposure to chlorinated hydrocarbon solvents is associated with exocrine pancreatic cancer.

  19. Pancreatic Cancer, A Mis-interpreter of the Epigenetic Language.

    Science.gov (United States)

    Iguchi, Eriko; Safgren, Stephanie L; Marks, David L; Olson, Rachel L; Fernandez-Zapico, Martin E

    2016-12-01

    Pancreatic cancer is the third leading cause of cancer mortality in the U.S. with close to 40,000 deaths per year. Pancreatic ductal adenocarcinoma (PDAC) represents approximately 90 percent of all pancreatic cancer cases and is the most lethal form of the disease. Current therapies for PDAC are ineffective and most patients cannot be treated by surgical resection. Most research efforts have primarily focused on how genetic alterations cause, alter progression, contribute to diagnosis, and influence PDAC management. Over the past two decades, a model has been advanced of PDAC initiation and progression as a multi-step process driven by the acquisition of mutations leading to loss of tumor suppressors and activation of oncogenes. The recognition of the essential roles of these genetic alterations in the development of PDAC has revolutionized our knowledge of this disease. However, none of these findings have turned into effective treatment for this dismal malignancy. In recent years, studies in the areas of chromatin modifications, and non-coding RNAs have uncovered mechanisms for regulating gene expression which occur independently of genetic alterations. Chromatin-based mechanisms are interwoven with microRNA-driven regulation of protein translation to create an integrated epigenetic language, which is grossly dysregulated in PDAC. Thus in PDAC, key tumor suppressors that are well established to play a role in PDAC may be repressed, and oncogenes can be upregulated secondary to epigenetic alterations. Unlike mutations, epigenetic changes are potentially reversible. Given this feature of epigenetic mechanisms, it is conceivable that targeting epigenetic-based events promoting and maintaining PDAC could serve as foundation for the development of new therapeutic and diagnostic approaches for this disease.

  20. Significant association between ABO blood group and pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    Julia; B; Greer; Mark; H; Yazer; Jay; S; Raval; M; Michael; Barmada; Randall; E; Brand; David; C; Whitcomb

    2010-01-01

    AIM:To evaluate whether the ABO blood group is related to pancreatic cancer risk in the general population of the United States.METHODS:Using the University of Pittsburgh's clinicalpancreatic cancer registry,the blood donor database from our local blood bank (Central Blood Bank),and the blood product recipient database from the regional transfusion service (Centralized Transfusion Service) in Pittsburgh,Pennsylvania,we identified 274 pancreatic cancer patients with previously determined serological ABO bloo...

  1. Invasion and metastasis in pancreatic cancer.

    Science.gov (United States)

    Keleg, Shereen; Büchler, Peter; Ludwig, Roman; Büchler, Markus W; Friess, Helmut

    2003-01-22

    Pancreatic cancer remains a challenging disease with an overall cumulative 5-year survival rate below 1%. The process of cancer initiation, progression and metastasis is still not understood well. Invasion and tumor metastasis are closely related and both occur within a tumour-host microecology, where stroma and tumour cells exchange enzymes and cytokines that modify the local extracellular matrix, stimulate cell migration, and promote cell proliferation and tumor cell survival. During the last decade considerable progress has been made in understanding genetic alterations of genes involved in local and systemic tumor growth. The most important changes occur in genes which regulate cell cycle progression, extracellular matrix homeostasis and cell migration. Furthermore, there is growing evidence that epigenetic factors including angiogenesis and lymphangiogenesis may participate in the formation of tumor metastasis. In this review we highlight the most important genetic alterations involved in tumor invasion and metastasis and further outline the role of tumor angiogenesis and lymphangiogenesis in systemic tumor dissemination.

  2. Pentoxifylline Treatment in Acute Pancreatitis (AP)

    Science.gov (United States)

    2016-09-14

    Acute Pancreatitis (AP); Gallstone Pancreatitis; Alcoholic Pancreatitis; Post-ERCP/Post-procedural Pancreatitis; Trauma Acute Pancreatitis; Hypertriglyceridemia Acute Pancreatitis; Idiopathic (Unknown) Acute Pancreatitis; Medication Induced Acute Pancreatitis; Cancer Acute Pancreatitis; Miscellaneous (i.e. Acute on Chronic Pancreatitis)

  3. Involvement of eicosanoids in the pathogenesis of pancreatic cancer: the roles of cyclooxygenase-2 and 5-lipoxygenase.

    Science.gov (United States)

    Knab, Lawrence M; Grippo, Paul J; Bentrem, David J

    2014-08-21

    The interplay between inflammation and cancer progression is a growing area of research. A combination of clinical, epidemiological, and basic science investigations indicate that there is a relationship between inflammatory changes in the pancreas and neoplastic progression. Diets high in ω-6 polyunsaturated fatty acids provide increased substrate for arachidonic acid metabolism by cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX) to form eicosanoids. These eicosanoids directly contribute to pancreatic cancer cell proliferation. Both COX-2 and 5-LOX are upregulated in multiple cancer types, including pancreatic cancer. In vitro studies using pancreatic cancer cell lines have demonstrated upregulation of COX-2 and 5-LOX at both the mRNA and protein levels. When COX-2 and 5-LOX are blocked via a variety of mechanisms, cancer cell proliferation is abrogated both in vitro and in vivo. The mechanism of COX-2 has been shown to include effects on apoptosis as well as angiogenesis. 5-LOX has been implicated in apoptosis. The use of COX-2 and 5-LOX inhibitors in clinical studies in patients with pancreatic cancer has been limited. Patient enrollment has been restricted to those with advanced disease which makes evaluation of these drugs as chemopreventive agents difficult. COX-2 and 5-LOX expression have been shown to be present during the early neoplastic changes of pancreatic cancer, well before progression to invasive disease. This indicates that the ideal role for these interventions is early in the disease process as preventive agents, perhaps in patients with chronic pancreatitis or hereditary pancreatitis.

  4. The Notch Pathway Is Important in Maintaining the Cancer Stem Cell Population in Pancreatic Cancer

    OpenAIRE

    Abel, Ethan V.; Kim, Edward J.; Jingjiang Wu; Mark Hynes; Filip Bednar; Erica Proctor; Lidong Wang; Dziubinski, Michele L; Simeone, Diane M.

    2014-01-01

    Background Pancreatic cancer stem cells (CSCs) represent a small subpopulation of pancreatic cancer cells that have the capacity to initiate and propagate tumor formation. However, the mechanisms by which pancreatic CSCs are maintained are not well understood or characterized. Methods Expression of Notch receptors, ligands, and Notch signaling target genes was quantitated in the CSC and non-CSC populations from 8 primary human pancreatic xenografts. A gamma secretase inhibitor (GSI) that inhi...

  5. Screening and surveillance approaches in familial pancreatic cancer.

    Science.gov (United States)

    Canto, Marcia Irene

    2008-07-01

    Screening and surveillance for pancreatic cancer and its precursors is a relatively new indication for endoscopic ultrasound. It provides an alternative approach to the ineffective treatment of mostly incurable symptomatic pancreatic cancer. It is currently reserved for individuals with an increased risk for pancreatic ductal adenocarcinoma, such as those who have inherited genetic syndromes (eg, patients who have Peutz-Jeghers syndrome or hereditary pancreatitis, germline mutation carriers of p16 and BRCA2) and at-risk relatives of patients who have familial pancreatic cancer. This article discusses the rationale for performing screening and surveillance, the types of patients who are eligible for screening, the diagnostic modalities and technique for screening, the diagnostic yield of screening, and the ongoing research.

  6. Role of endoscopic ultrasound in the molecular diagnosis of pancreatic cancer

    Science.gov (United States)

    Bournet, Barbara; Gayral, Marion; Torrisani, Jérôme; Selves, Janick; Cordelier, Pierre; Buscail, Louis

    2014-01-01

    Pancreatic ductal adenocarcinoma remains one of the most deadly types of tumor. Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is a safe, cost-effective, and accurate technique for evaluating and staging pancreatic tumors. However, EUS-FNA may be inconclusive or doubtful in up to 20% of cases. This review underlines the clinical interest of the molecular analysis of samples obtained by EUS-FNA in assessing diagnosis or prognosis of pancreatic cancer, especially in locally advanced tumors. On EUS-FNA materials DNA, mRNA and miRNA can be extracted, amplified, quantified and subjected to methylation assay. Kras mutation assay, improves diagnosis of pancreatic cancer. When facing to clinical and radiological presentations of pseudo-tumorous chronic pancreatitis, wild-type Kras is evocative of benignity. Conversely, in front of a pancreatic mass suspected of malignancy, a mutated Kras is highly evocative of pancreatic adenocarcinoma. This strategy can reduce false-negative diagnoses, avoids the delay of making decisions and reduces loss of surgical resectability. Similar approaches are conducted using analysis of miRNA expression as well as Mucin or markers of invasion (S100P, S100A6, PLAT or PLAU). Beyond the diagnosis approach, the prediction of response to treatment can be also investigated form biomarkers expression within EUS-FNA materials. PMID:25152579

  7. The Smad family and its role in pancreatic cancer.

    Science.gov (United States)

    Singh, P; Wig, J D; Srinivasan, R

    2011-01-01

    One of the major signaling pathways that determine the tumor aggression and patient outcome in pancreatic cancer is the transforming growth factor-beta (TGF-ß) pathway. It is inactivated at various levels in pancreatic cancer and plays a dual role in tumor initiation and progression. The Smad family of proteins transduce signals from the TGF-ß superfamily ligands that regulate cell proliferation, differentiation and death through activation of receptor serine/threonine kinases. This review discusses the structure, function and regulation of various participating Smad family members, and their individual roles in determining the progression and outcome of pancreatic cancer patients, with a special emphasis on Smad4.

  8. Organoid Models of Human and Mouse Ductal Pancreatic Cancer

    NARCIS (Netherlands)

    Boj, Sylvia F.; Hwang, Chang-Il; Baker, Lindsey A.; Chio, Iok In Christine; Engle, Dannielle D.; Corbo, Vincenzo; Jager, Myrthe; Ponz-Sarvise, Mariano; Tiriac, Herve; Spector, Mona S.; Gracanin, Ana; Oni, Tobiloba; Yu, Kenneth H.; van Boxtel, Ruben; Huch, Meritxell; Rivera, Keith D.; Wilson, John P.; Feigin, Michael E.; Oehlund, Daniel; Handly-Santana, Abram; Ardito-Abraham, Christine M.; Ludwig, Michael; Elyada, Ela; Alagesan, Brinda; Biffi, Giulia; Yordanov, Georgi N.; Delcuze, Bethany; Creighton, Brianna; Wright, Kevin; Park, Youngkyu; Morsink, Folkert H. M.; Molenaar, IQ; Borel Rinkes, Inne H.; Cuppen, Edwin; Hao, Yuan; Jin, Ying; Nijman, Isaac J.; Iacobuzio-Donahue, Christine; Leach, Steven D.; Pappin, Darryl J.; Hammell, Molly; Klimstra, David S.; Basturk, Olca; Hruban, Ralph H.; Offerhaus, George Johan; Vries, Robert G. J.; Clevers, Hans; Tuveson, David A.

    2015-01-01

    Pancreatic cancer is one of the most lethal malignancies due to its late diagnosis and limited response to treatment. Tractable methods to identify and interrogate pathways involved in pancreatic tumorigenesis are urgently needed. We established organoid models from normal and neoplastic murine and

  9. Organoid models of human and mouse ductal pancreatic cancer

    NARCIS (Netherlands)

    Boj, Sylvia F; Hwang, Chang-Il; Baker, Lindsey A; Chio, Iok In Christine; Engle, Dannielle D; Corbo, Vincenzo; Jager, Myrthe; Ponz-Sarvise, Mariano; Tiriac, Hervé; Spector, Mona S; Gracanin, Ana; Oni, Tobiloba; Yu, Kenneth H; van Boxtel, Ruben; Huch, Meritxell; Rivera, Keith D; Wilson, John P; Feigin, Michael E; Öhlund, Daniel; Handly-Santana, Abram; Ardito-Abraham, Christine M; Ludwig, Michael; Elyada, Ela; Alagesan, Brinda; Biffi, Giulia; Yordanov, Georgi N; Delcuze, Bethany; Creighton, Brianna; Wright, Kevin; Park, Youngkyu; Morsink, Folkert H M; Molenaar, I Quintus; Borel Rinkes, Inne H; Cuppen, Edwin; Hao, Yuan; Jin, Ying; Nijman, Isaac J; Iacobuzio-Donahue, Christine; Leach, Steven D; Pappin, Darryl J; Hammell, Molly; Klimstra, David S; Basturk, Olca; Hruban, Ralph H; Offerhaus, George Johan; Vries, Robert G J; Clevers, Hans; Tuveson, David A

    2015-01-01

    Pancreatic cancer is one of the most lethal malignancies due to its late diagnosis and limited response to treatment. Tractable methods to identify and interrogate pathways involved in pancreatic tumorigenesis are urgently needed. We established organoid models from normal and neoplastic murine and

  10. 白蛋白结合型紫杉醇治疗晚期胰腺癌的临床观察%The clinical observation of albumin-bound paclitaxel combined chemotherapy scheme in advanced pan-creatic cancer

    Institute of Scientific and Technical Information of China (English)

    尹敏; 仲悦娇; 袁渊; 沈波

    2016-01-01

    目的:探讨白蛋白结合型紫杉醇治疗晚期胰腺癌患者的临床疗效及不良反应。方法选择2010年8月至2014年7月就诊于南京医科大学附属肿瘤医院的35例晚期转移性胰腺癌患者,均以白蛋白结合型紫杉醇为基础药物的联合化疗方案治疗,回顾性分析其治疗效果和安全性。结果35例患者均可评估疗效。无完全缓解( CR)病例,13例部分缓解( PR),16例疾病稳定( SD),6例疾病进展( PD)。其中,一线治疗中7例PR,5例SD;二线治疗中4例PR,7例SD;二线以上治疗中4例SD。一线治疗的中位无进展生存期(mPFS)为7.1个月,二线治疗的mPFS为4.8个月,二线以上治疗的mPFS为5.3个月。主要不良反应为脱发、血液毒性、肝功能损伤、消化道反应等,经对症处理后均好转。结论白蛋白结合型紫杉醇联合化疗治疗晚期胰腺癌疗效肯定,耐受性良好,值得进一步研究。%Objective To investigate the efficacy and adverse reactions of albumin-bound paclitaxel com-bined chemotherapy scheme in advanced pancreatic cancer. Methods 35 patients with advanced pancreatic cancer were treated from August 2010 to July 2014 in the Affiliated Jiangsu Cancer Hospital of NJMU. All of these patients were treated with albumin bound-paclitaxel combined chemotherapy scheme (200~260 mg/m2). After 2 cycles of chemotherapy treatment, the recent curative effects were evaluated according to RECIST crite-ria, the efficacy and adverse reactions were evaluated according to the NCI CTC 3. 0 standard. Results The curative effect of 35 patients can be evaluated reasonably. There are no complete remission ( CR) , 13 cases of partial response ( PR) 16 cases of stable disease ( SD) 6 cases of disease progression ( PD) . There are 7 cases of PR, 5 cases of SD, and 7. 1 months of mPFS in the first line therapy;4 cases of PR, 7 cases of SD, and 4. 8 months of mPFS in the second line therapy;4 cases of SD, 5. 3 months of mPFS in the third line

  11. Long-Time Survival of a Patient with Metastatic Pancreatic Cancer: A Case Report

    Directory of Open Access Journals (Sweden)

    Željko Soldić

    2011-08-01

    Full Text Available Pancreatic cancer is a malignant neoplasm of the pancreas. It does not cause any symptoms in the early stage, and later symptoms are nonspecific, thus the disease is usually diagnosed when already advanced. In 2008, pancreatic cancer ranked eighth on the list of the 10 most common cancers among men in Croatia and tenth on the list of the most common cancers among Croatian women. Pancreatic cancer has a poor prognosis, with a survival time of only 6–8 months for metastatic disease. Gemcitabine is the standard chemotherapeutic option. Other chemotherapeutic agents include5-fluorouracil and leucovorin. In this paper, we present a case of a patient diagnosed with locally advanced and metastatic pancreatic cancer, who is still alive and currently receives his fourth line of chemotherapy 5 years after the diagnosis. Following disease progression on gemcitabine chemotherapy, he was treated with chemoradiotherapy which, however, had no effect. We then applied cisplatin monochemotherapy which offered excellent disease control, was well tolerated by the patient and, although somewhat obsolete in this form, showed to be a valuable chemotherapeutic option.

  12. Blood Type Influences Pancreatic Cancer Risk | Division of Cancer Prevention

    Science.gov (United States)

    A variation in the gene that determines ABO blood type influences the risk of pancreatic cancer, according to the results of the first genome-wide association study (GWAS) for this highly lethal disease. The genetic variation, a single nucleotide polymorphism (SNP), was discovered in a region of chromosome 9 that harbors the gene that determines blood type, the researchers reported August 2 online in Nature Genetics. |

  13. Values of mutations of K-ras oncogene at codon 12 in detection of pancreatic cancer:15-year experience

    Institute of Scientific and Technical Information of China (English)

    De-Qing Mu; You-Shu Peng; Qiao-Jian Xu

    2004-01-01

    AIM: To summarize progress in the study of K-ras gene studies in pancreatic cancer and its potential clinical significance in screening test for early detection of pancreatic cancer, and to differentiate pancreatic cancer from chronic pancreatitis in recent decade.METHODS: Literature search (MEDLINE 1986-2003) was performed using the key words K-ras gene, pancreatic cancer, chronic pancreatitis, and diagnosis. Two kind of opposite points of view on the significance of K-ras gene in detection early pancreatic cancer and differentiation pancreatic cancer from chronic pancreatitis were investigated.The presence of a K-ras gene mutation at codon 12 has been seen in 75-100% of pancreatic cancers, and is not rare in patients with chronic pancreatitis, and represents an increased risk of developing pancreatic cancer. However, the significance of the detection of this mutation in specimens obtained by needle aspiration from pure pancreatic juice and from stools for its utilization for the detection of early pancreatic cancer, and differentiation pancreatic cancer from chronic pancreatitis remains controversial. CONCLUSION: The value of K-ras gene mutation for the detection of early pancreatic cancer and differentiation pancreatic cancer from chronic pancreatitis remains uncertains in clinical pratice. Nevertheless, K-ras mutation screening may increase the sensitivity of FNA and ERP cytology and may be useful in identifying pancreatitis patients at high risk for developing cancer, and as a adjunct with cytology to differentiate pancreatic cancer from chronic pancreatitis.

  14. Acute Recurrent Pancreatitis: A Possible Clinical Manifestation of Ampullary Cancer

    Directory of Open Access Journals (Sweden)

    Athanasios Petrou

    2011-11-01

    Full Text Available Context Acute recurrent pancreatitis still poses diagnostic difficulties. The coexistence or moreover the causative relationship of carcinoma of the ampulla of Vater and acute recurrent pancreatitis is fairly rare. Case report We present a case of carcinoma of the ampulla of Vater that presented with acute recurrent necrotizing pancreatitis complicated with pseudocysts. A diagnosis of malignancy in the ampulla was only made after several ERCP attempts due to residual inflammation at the periampullary area. Conclusion Malignancy at the ampulla of Vater causing recurrent episodes of pancreatitis represents a realistic risk and attempts to diagnose the underlying cause should always take into account the possibility of cancer.

  15. ANTI CANCER ACTIVITY OF PHYLLANTHUS AMARUS IN AZASERINE INDUCED PANCREATIC CANCER OF WISTAR RATS

    Directory of Open Access Journals (Sweden)

    Ankit Prajapati

    2015-06-01

    Full Text Available Pancreatic cancer is a malignant neoplasm originating from transformed cells arising in tissues forming the pancreas. The most common type of pancreatic cancer is adeno-carcinoma. The present experiment was carried out to study histopathological changes occur in pancreas in different groups of azaserine induced pancreatic cancer in Wistar rats with and without the treatment of aqueous and alcoholic extract of Phyllanthus amarus at different doses. Histopathological examination of pancreas of untreated group of rats showed hyperplasia of pancreatic duct, necrosis, fatty changes, haemorrhages between pancreatic cells. The rats treated with Phyllanthus amarus extracts showed no pathological lesions.

  16. Chronic stress accelerates pancreatic cancer growth and invasion: a critical role for beta-adrenergic signaling in the pancreatic microenvironment.

    Science.gov (United States)

    Kim-Fuchs, Corina; Le, Caroline P; Pimentel, Matthew A; Shackleford, David; Ferrari, Davide; Angst, Eliane; Hollande, Frédéric; Sloan, Erica K

    2014-08-01

    Pancreatic cancer cells intimately interact with a complex microenvironment that influences pancreatic cancer progression. The pancreas is innervated by fibers of the sympathetic nervous system (SNS) and pancreatic cancer cells have receptors for SNS neurotransmitters which suggests that pancreatic cancer may be sensitive to neural signaling. In vitro and non-orthotopic in vivo studies showed that neural signaling modulates tumour cell behavior. However the effect of SNS signaling on tumor progression within the pancreatic microenvironment has not previously been investigated. To address this, we used in vivo optical imaging to non-invasively track growth and dissemination of primary pancreatic cancer using an orthotopic mouse model that replicates the complex interaction between pancreatic tumor cells and their microenvironment. Stress-induced neural activation increased primary tumor growth and tumor cell dissemination to normal adjacent pancreas. These effects were associated with increased expression of invasion genes by tumor cells and pancreatic stromal cells. Pharmacological activation of β-adrenergic signaling induced similar effects to chronic stress, and pharmacological β-blockade reversed the effects of chronic stress on pancreatic cancer progression. These findings indicate that neural β-adrenergic signaling regulates pancreatic cancer progression and suggest β-blockade as a novel strategy to complement existing therapies for pancreatic cancer.

  17. Tea drinking and risk of pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    Wei Junbao; Chen Long; Zhu Xiaodong

    2014-01-01

    Background Epidemiologic studies have reported inconsistent results regarding tea consumption and the risk of pancreatic cancer.This study aimed to investigate whether tea consumption is related to the risk of pancreatic cancer.Methods We searched Medline,EMBASE,ISI Web of Science,and the Cochrane library for studies published up to November 2013.We used a meta-analytic approach to estimate overall odds ratio (OR) and 95% confidence interval (CI) for the highest versus the lowest tea consumption categories.Results The summary OR for high versus no/almost never tea drinkers was 1.04 (95% CI:0.91-1.20),with no significant heterogeneity across studies (P=0.751;I2=0.0%).The OR was 0.99 (95% CI:0.77-1.28) in males and 1.01 (95% CI:0.79-1.29) in females.The OR was 1.07 (95% CI:0.85-1.34) in Asian studies,1.05 (95% CI:0.84-1.31) in European studies,and 0.98 (95% CI:0.72-1.34) in the US studies.The OR was 0.87 (95% CI:0.69-1.10) without adjustment for a history of diabetes and 1.16 (95% CI:0.97-0.39) after adjustment for a history of diabetes.The OR was 0.90 (95% CI:0.72-1.12) without adjustment for alcohol drinking and 1.16 (95% CI:0.96-1.39) after adjustment for alcohol drinking.The OR was 0.97 (95% CI:0.76-1.25) without adjustment for BMI and 1.07 (95% CI:0.87-1.31) after adjustment for BMI.Conclusion This systematic meta-analysis of cohort studies dose not provide quantitative evidence that tea consumption is appreciably related to the risk of pancreatic cancer,even at high doses.

  18. MicroRNA-gene signaling pathways in pancreatic cancer

    Directory of Open Access Journals (Sweden)

    Alexandra Drakaki

    2013-10-01

    Full Text Available Pancreatic cancer is the fourth most frequent cause of cancer-related deaths and is characterized by early metastasis and pronounced resistance to chemotherapy and radiation therapy. Despite extensive esearch efforts, there is not any substantial progress regarding the identification of novel drugs against pancreatic cancer. Although the introduction of the chemotherapeutic agent gemcitabine improved clinical response, the prognosis of these patients remained extremely poor with a 5-year survival rate of 3-5%. Thus, the identification of the novel molecular pathways involved in pancreatic oncogenesis and the development of new and potent therapeutic options are highly desirable. Here, we describe how microRNAs control signaling pathways that are frequently deregulated during pancreatic oncogenesis. In addition, we provide evidence that microRNAs could be potentially used as novel pancreatic cancer therapeutics through reversal of chemotherapy and radiotherapy resistance or regulation of essential molecular pathways. Further studies should integrate the deregulated genes and microRNAs into molecular networks in order to identify the central regulators of pancreatic oncogenesis. Targeting these central regulators could lead to the development of novel targeted therapeutic approaches for pancreatic cancer patients.

  19. Is Type 2 Diabetes a Risk Factor for Pancreatic Cancer?

    Directory of Open Access Journals (Sweden)

    Raffaele Pezzilli

    2009-11-01

    Full Text Available The relationship between diabetes mellitus and the risk of pancreatic cancer has been a matter of study for a long time. Taking into consideration diabetes mellitus irrespective of type, there is a lack of agreement regarding the data; in fact, some epidemiological studies have excluded this possibility whereas others have found a relationship between the presence of diabetes and the development of pancreatic cancer. On the other hand, a recent study has reported that metformin may have a protective effect on the development of pancreatic cancer [1]. Therefore, we would briefly revise the data both for and against the possibility that pancreatic cancer is a consequence of long-standing diabetes.

  20. Nab-Paclitaxel Plus Gemcitabine for Metastatic Pancreatic Cancer

    Science.gov (United States)

    A summary of results from a phase III trial that compared the combination of albumin-bound paclitaxel (nab-paclitaxel [Abraxane®]) and gemcitabine (Gemzar®) versus gemcitabine alone in patients with metastatic pancreatic cancer.

  1. Islet Inflammation: A Causal Link Between Diabetes and Pancreatic Cancer?

    Directory of Open Access Journals (Sweden)

    Peter Butler

    2014-09-01

    Full Text Available Type 2 diabetes (T2DM is characterized hyperglycemia due to impaired insulin secretion and a deficit of pancreatic beta cells in the setting of insulin resistance. Most individuals are able to compensate for insulin resistance by increasing insulin secretion so the genetic basis of T2DM appears to be linked to the underlying mechanisms leading to this abnormal pancreatic islet response to insulin resistance. In support of this, pancreatic islets in T2DM have a specific pathology. The ~65% deficit in beta cells is presumably due to increased beta cell apoptosis, the underlying mechanisms of which include a misfolded protein induced endoplasmic reticulum stress, mitochondrial dysfunction and local release of inflammatory cytokines. It has long been recognized that there is an association between T2DM and pancreatic cancer. One explanation for this is the development of diabetes in relation to pancreatic cancer, when the diagnoses are temporarily related.

  2. Recent developments in palliative chemotherapy for locally advanced and metastatic pancreas cancer

    Institute of Scientific and Technical Information of China (English)

    Soley; Bayraktar; Ulas; Darda; Bayraktar; Caio; Max; Rocha-Lima

    2010-01-01

    In spite of advances made in the management of the other more common cancers of the gastrointestinal tract,significant progress in the treatment of pancreatic cancer remains elusive.Nearly as many deaths occur from pancreatic cancer as are diagnosed each year reflecting the poor prognosis typically associated with this disease.Until recently,the only treatment with an impact on survival was surgery.In the palliative setting,gemcitabine(Gem) has been a standard treatment for advanced pancreatic cancer since ...

  3. Is Type 2 Diabetes a Risk Factor for Pancreatic Cancer?

    OpenAIRE

    Raffaele Pezzilli; Antonio Maria Morselli-Labate; Riccardo Casadei

    2009-01-01

    The relationship between diabetes mellitus and the risk of pancreatic cancer has been a matter of study for a long time. Taking into consideration diabetes mellitus irrespective of type, there is a lack of agreement regarding the data; in fact, some epidemiological studies have excluded this possibility whereas others have found a relationship between the presence of diabetes and the development of pancreatic cancer. On the other hand, a recent study has reported that metformin may have a pro...

  4. Overexpression of c-met in the early stage of pancreatic carcinogenesis; altered expression is not sufficient for progression from chronic pancreatitis to pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    Jun Yu; Eishi Nagai; Masao Tanaka; Kenoki Ohuchida; Kazuhiro Mizumoto; Nami Ishikawa; Yasuhiro Ogura; Daisuke Yamada; Takuya Egami; Hayato Fujita; Seiji Ohashi

    2006-01-01

    AIM: To investigate c-met expression during early pancreatic carcinogenesis.METHODS: We used 46 bulk tissues and 36 microdissected samples, including normal pancreas, chronic pancreatitis, and pancreatic cancer, for quantitative real time reverse transcription-polymerase chain reaction.RESULTS: In bulk tissue analyses, pancreatic cancer tissues expressed significantly higher levels of c-met than did chronic pancreatitis and normal pancreas tissues.c-met levels did not differ between chronic pancreatitis and normal pancreas tissues. In microdissection-based analyses, c-met was expressed at higher levels in microdissected pancreatic cancer cells and pancreatitisaffected epithelial cells than in normal ductal epithelial cells (both, P < 0.01). Interestingly, pancreatitis-affected epithelial cells expressed levels of c-met similar to those of pancreatic cancer cells.CONCLUSION: Overexpression of c-met occurs during the early stage of pancreatic carcinogenesis, and a single alteration of c-met expression is not sufficient for progression of chronic pancreatitis-affected epithelial cells to pancreatic cancer cells.

  5. Family history of cancer and risk of Pancreatic Cancer: A Pooled Analysis from the Pancreatic Cancer Cohort Consortium (PanScan)

    Science.gov (United States)

    Jacobs, Eric J.; Chanock, Stephen J.; Fuchs, Charles S.; LaCroix, Andrea; McWilliams, Robert R.; Steplowski, Emily; Stolzenberg-Solomon, Rachael Z.; Arslan, Alan A.; Bueno-de-Mesquita, H. Bas; Gross, Myron; Helzlsouer, Kathy; Petersen, Gloria; Zheng, Wei; Agalliu, Ilir; Allen, Naomi E.; Amundadottir, Laufey; Boutron-Ruault, Marie-Christine; Buring, Julie E.; Canzian, Federico; Clipp, Sandra; Dorronsoro, Miren; Gaziano, J. Michael; Giovannucci, Edward L.; Hankinson, Susan E.; Hartge, Patricia; Hoover, Robert N.; Hunter, David J.; Jacobs, Kevin B.; Jenab, Mazda; Kraft, Peter; Kooperberg, Charles; Lynch, Shannon M.; Sund, Malin; Mendelsohn, Julie B.; Mouw, Tracy; Newton, Christina C.; Overvad, Kim; Palli, Domenico; Peeters, Petra H.M.; Rajkovic, Aleksandar; Shu, Xiao-Ou; Thomas, Gilles; Tobias, Geoffrey S.; Trichopoulos, Dimitrios; Virtamo, Jarmo; Wactawski-Wende, Jean; Wolpin, Brian M.; Yu, Kai; Zeleniuch-Jacquotte, Anne

    2010-01-01

    A family history of pancreatic cancer has consistently been associated with increased risk of pancreatic cancer. However, uncertainty remains about the strength of this association. Results from previous studies suggest a family history of select cancers (i.e. ovarian, breast, and colorectal) could also be associated, although not as strongly, with increased risk of pancreatic cancer. We examined the association between a family history of five types of cancer (pancreas, prostate, ovarian, breast, and colorectal) and risk of pancreatic cancer using data from a collaborative nested case-control study conducted by the Pancreatic Cancer Cohort Consortium. Cases and controls were from cohort studies from the United States, Europe, and China, and a case-control study from the Mayo Clinic. Analyses of family history of pancreatic cancer included 1,183 cases and 1,205 controls. A family history of pancreatic cancer in a parent, sibling, or child was associated with increased risk of pancreatic cancer (multivariate-adjusted OR = 1.76, 95% CI 1.19–2.61). A family history of prostate cancer was also associated with increased risk (OR = 1.45, 95% CI 1.12–1.89). There were no statistically significant associations with a family history of ovarian cancer (OR = 0.82, 95% CI 0.52–1.31), breast cancer (OR = 1.21, 95% CI 0.97–1.51), or colorectal cancer (OR = 1.17, 95% CI 0.93–1.47). Our results confirm a moderate sized association between a family history of pancreatic cancer and risk of pancreatic cancer and also provide evidence for an association with a family history of prostate cancer worth further study. PMID:20049842

  6. Family history of cancer and risk of pancreatic cancer : a pooled analysis from the Pancreatic Cancer Cohort Consortium (PanScan)

    NARCIS (Netherlands)

    Jacobs, Eric J.; Chanock, Stephen J.; Fuchs, Charles S.; LaCroix, Andrea; McWilliams, Robert R.; Steplowski, Emily; Stolzenberg-Solomon, Rachael Z.; Arslan, Alan A.; Bueno-de-Mesquita, H. Bas; Gross, Myron; Helzlsouer, Kathy; Petersen, Gloria; Zheng, Wei; Agalliu, Ilir; Allen, Naomi E.; Amundadottir, Laufey; Boutron-Ruault, Marie-Christine; Buring, Julie E.; Canzian, Federico; Clipp, Sandra; Dorronsoro, Miren; Gaziano, J. Michael; Giovannucci, Edward L.; Hankinson, Susan E.; Hartge, Patricia; Hoover, Robert N.; Hunter, David J.; Jacobs, Kevin B.; Jenab, Mazda; Kraft, Peter; Kooperberg, Charles; Lynch, Shannon M.; Sund, Malin; Mendelsohn, Julie B.; Mouw, Tracy; Newton, Christina C.; Overvad, Kim; Palli, Domenico; Peeters, Petra H. M.; Rajkovic, Aleksandar; Shu, Xiao-Ou; Thomas, Gilles; Tobias, Geoffrey S.; Trichopoulos, Dimitrios; Virtamo, Jarmo; Wactawski-Wende, Jean; Wolpin, Brian M.; Yu, Kai; Zeleniuch-Jacquotte, Anne

    2010-01-01

    A family history of pancreatic cancer has consistently been associated with increased risk of pancreatic cancer. However, uncertainty remains about the strength of this association. Results from previous studies suggest a family history of select cancers (i.e., ovarian, breast and colorectal) could

  7. Parenteral nutrition support for patients with pancreatic cancer. Results of a phase II study

    OpenAIRE

    Riess Hanno; Doerken Bernd; Stieler Jens; Gövercin Mehmet; Arnold Dirk; Pelzer Uwe; Oettle Helmut

    2010-01-01

    Abstract Background Cachexia is a common problem in patients (pts) suffering from upper gastrointestinal cancer. In addition, most of these patients suffer from malabsorption and stenosis of the gastrointestinal tract due to their illness. Various methods of supplementary nutrition (enteral, parenteral) are practised. In patients with advanced pancreatic cancer (APC), phase angle, determined by bio-electrical impedance analysis (BIA), seems to be a survival predictor. The positive influence o...

  8. Ligands for peroxisome proliferator-activated receptor gamma inhibit growth of pancreatic cancers both in vitro and in vivo.

    Science.gov (United States)

    Itami, A; Watanabe, G; Shimada, Y; Hashimoto, Y; Kawamura, J; Kato, M; Hosotani, R; Imamura, M

    2001-11-01

    Peroxisome proliferator-activated receptor gamma (PPARgamma) is expressed largely in adipose tissues and plays an important role in adipocyte differentiation. Several studies have recently shown that ligands of PPARgamma could lead to growth inhibition in some malignancies. In our study, we focused on pancreatic cancers, because the prognosis of advanced pancreatic cancer has not significantly improved due to its resistance to various chemotherapeutic regimens, so that a novel strategy should be required. We show here that PPARgamma is expressed in 5 pancreatic cancer cell lines detected in both mRNA and protein level as well as in human primary and metastatic pancreatic carcinomas examined by immunohistochemical studies. A specific ligand of PPARgamma, troglitazone, led to G1 accumulation with the increase in p27(Kip1), but not p21(Waf1/Cip1) and inhibited cellular proliferation in a pancreatic cancer cell line, Panc-1. The overexpression of PPARgamma in a pancreatic cancer cell line, KMP-3, caused lipid accumulation, which suggested cell growth in some cancers might be inhibited, at least in part, through terminal differentiation in the adipogenic lineage. In addition, implanted Panc-1 tumors in nude mice showed significant inhibition of tumor growth, when treated with pioglitazone, another specific ligand of PPARgamma. Our results suggest that ligands of PPARgamma may be a novel therapeutic agent for the treatment of pancreatic carcinomas.

  9. ANTI CANCER ACTIVITY OF PHYLLANTHUS AMARUS IN AZASERINE INDUCED PANCREATIC CANCER OF WISTAR RATS

    OpenAIRE

    Ankit Prajapati; Sunant Raval; TapanVaria

    2015-01-01

    Pancreatic cancer is a malignant neoplasm originating from transformed cells arising in tissues forming the pancreas. The most common type of pancreatic cancer is adeno-carcinoma. The present experiment was carried out to study histopathological changes occur in pancreas in different groups of azaserine induced pancreatic cancer in Wistar rats with and without the treatment of aqueous and alcoholic extract of Phyllanthus amarus at different doses. Histopathological examination of ...

  10. Screening Technologies for Target Identification in Pancreatic Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Michl, Patrick, E-mail: michlp@med.uni-marburg.de; Ripka, Stefanie; Gress, Thomas; Buchholz, Malte [Department of Gastroenterology and Endocrinology, University Hospital, Philipps-University Marburg, Baldinger Strasse, D-35043 Marburg (Germany)

    2010-12-29

    Pancreatic cancer exhibits an extraordinarily high level of resistance to almost any kind of systemic therapy evaluated in clinical trials so far. Therefore, the identification of novel therapeutic targets is urgently required. High-throughput screens have emerged as an important tool to identify putative targets for diagnosis and therapy in an unbiased manner. More than a decade ago, microarray technology was introduced to identify differentially expressed genes in pancreatic cancer as compared to normal pancreas, chronic pancreatitis and other cancer types located in close proximity to the pancreas. In addition, proteomic screens have facilitated the identification of differentially secreted proteins in body fluids of pancreatic cancer patients, serving as possible biomarkers. Recently, RNA interference-based loss-of-function screens have been used to identify functionally relevant genes, whose knock-down has impact on pancreatic cancer cell viability, thereby representing potential new targets for therapeutic intervention. This review summarizes recent results of transcriptional, proteomic and functional screens in pancreatic cancer and discusses potentials and limitations of the respective technologies as well as their impact on future therapeutic developments.

  11. Dietary Patterns and Pancreatic Cancer Risk: A Meta-Analysis.

    Science.gov (United States)

    Lu, Pei-Ying; Shu, Long; Shen, Shan-Shan; Chen, Xu-Jiao; Zhang, Xiao-Yan

    2017-01-05

    A number of studies have examined the associations between dietary patterns and pancreatic cancer risk, but the findings have been inconclusive. Herein, we conducted this meta-analysis to assess the associations between dietary patterns and the risk of pancreatic cancer. MEDLINE (provided by the National Library of Medicine) and EBSCO (Elton B. Stephens Company) databases were searched for relevant articles published up to May 2016 that identified common dietary patterns. Thirty-two studies met the inclusion criteria and were finally included in this meta-analysis. A reduced risk of pancreatic cancer was shown for the highest compared with the lowest categories of healthy patterns (odds ratio, OR = 0.86; 95% confidence interval, CI: 0.77-0.95; p = 0.004) and light-moderate drinking patterns (OR = 0.90; 95% CI: 0.83-0.98; p = 0.02). There was evidence of an increased risk for pancreatic cancer in the highest compared with the lowest categories of western-type pattern (OR = 1.24; 95% CI: 1.06-1.45; p = 0.008) and heavy drinking pattern (OR = 1.29; 95% CI: 1.10-1.48; p = 0.002). The results of this meta-analysis demonstrate that healthy and light-moderate drinking patterns may decrease the risk of pancreatic cancer, whereas western-type and heavy drinking patterns may increase the risk of pancreatic cancer. Additional prospective studies are needed to confirm these findings.

  12. Depression and Pancreatic Cancer: A Poorly Understood Link

    Directory of Open Access Journals (Sweden)

    Nektaria Makrilia

    2009-01-01

    Full Text Available Although pancreatic carcinoma and depression have been linked for many years, the prevalence and relationship of these two entities are still poorly understood. Published studies reviewing this issue have found that many patients with pancreatic cancer are depressed. A clinical gestalt asserts that many patients present with depression before pancreatic carcinoma is diagnosed. If the definition of depression is broadened to include mild depression in addition to major depression, these numbers may increase. Depression in pancreatic cancer is a condition that must be diagnosed and treated, as studies have shown that depression is a detrimental factor in the last stages of life of cancer patients as patients with high score of depression have worse survival rates in breast and hepatobiliary cancers. Treatment for depression has also been shown to impact quality of life and may bring increased comfort during end of life. This article reviews the literature linking pancreatic carcinoma to depression as well as the appropriate therapeutic approach. In addition, for the first time, it fully underlines the key role of a social worker as a key participant throughout the cancer continuum: at time of diagnosis, treatment, relapse, survivorship, end of life and bereavement in the management of pancreatic cancer patients.

  13. Qingyihuaji Formula Inhibits Pancreatic Cancer and Prolongs Survival by Downregulating Hes-1 and Hey-1

    Directory of Open Access Journals (Sweden)

    Yanli Xu

    2015-01-01

    Full Text Available The dire prognosis of pancreatic cancer has not markedly improved during past decades. The present study was carried out to explore the effect of Qingyihuaji formula (QYHJ on inhibiting pancreatic cancer and prolonging survival in related Notch signaling pathway. Proliferation of pancreatic cancer cells (SW1990 and PANC-1 was detected by MTT assay at 24, 48, and 72 h with exposure to various concentrations (0.08–50 mg/mL of QYHJ water extract. Pancreatic tumor models of nude mice were divided into three groups randomly (control, QYHJ, and gemcitabine. mRNA and protein expression of Notch target genes (Hes-1, Hey-1, Hey-2, and Hey-L in dissected tumor tissue were detected. Results showed that proliferation of SW1990 cells and PANC-1 cells was inhibited by QYHJ water extract in a dose-dependent and time-dependent manner. QYHJ effectively inhibited tumor growth and prolonged survival time in nude mice. Expression of both Hes-1 and Hey-1 was decreased significantly in QYHJ group, suggesting that Hes-1 and Hey-1 in Notch signaling pathway might be potential targets for QYHJ treatment. This research could help explain the clinical effectiveness of QYHJ and may provide advanced pancreatic cancer patients with a new therapeutic option.

  14. Mortality, Cancer, and Comorbidities Associated With Chronic Pancreatitis

    DEFF Research Database (Denmark)

    Bang, Ulrich Christian; Benfield, Thomas; Hyldstrup, Lars

    2014-01-01

    BACKGROUND & AIMS: We aimed to assess the risk of death, cancer, and comorbidities among patients with alcoholic and nonalcoholic chronic pancreatitis (CP). METHODS: We performed a nationwide retrospective cohort study, collecting data from Danish registries from 1995 through 2010. We evaluated...... cases (10.2%) and controls (3.3%). Cancer (particularly pancreatic cancer) was a frequent cause of death among cases; the HR was 6.9 (95% CI, 7.5-11.8). Alcoholic CP did not produce a higher risk for cancer or death than nonalcoholic CP. Cerebrovascular disease (HR, 1.3; 95% CI, 1.2-1.4), chronic...... on a Danish nationwide cohort study, individuals with CP are at higher risk for death from cancer (particularly pancreatic cancer) and have a higher incidence of comorbidities than people without CP....

  15. Chronic Pancreatitis, Type 3c Diabetes, and Pancreatic Cancer Risk

    Directory of Open Access Journals (Sweden)

    David C Whitcomb

    2014-09-01

    Full Text Available About half of all patients with chronic pancreatitis (CP develop diabetes mellitus (DM due to the loss of islet cell mass, not just beta cells as in Type 1 DM (T1DM, or due to insulin resistance, as in Type 2 DM (T2DM. Patients with DM from loss of islets due to pancreatic disease or resection are diagnosed with pancreatogenic or Type 3c DM (T3cDM. Patients with T3cDM also lose counter-regulatory hormones, such as glucagon and pancreatic polypeptide, and experience maldigestion associated with pancreatic exocrine insufficiency. Patients with T3cDM are therefore more susceptible to hypoglycemia and a mismatch (asynchrony between food ingestion and nutrient absorption. At the same time, the use of incretin therapy is likely useless, since maldigestion leads to the release of higher levels of hind gut hormones, including GLP1. Thus, T3cDM caused by CP or destruction of the islets involves a special class of potential risks and comorbidity that may be overlooked if the CP has not been diagnosed.

  16. A study of transarterial infusion chemotherapy of gemcitabine plus three dimensional conformal radiotherapy for local advanced pancreatic cancer%经动脉灌注健择化疗联合三维适形放射治疗局部晚期胰腺癌的临床研究

    Institute of Scientific and Technical Information of China (English)

    Zhaojun Ding; Yanwei Sun; Jiayun Zhou

    2007-01-01

    Objective:To evaluate Ihe clinical effect of transarterial infusion chemotherapy of gemcitabine plus three dimensional conformal radiotherapy on patients with local advanced pancreatic cancer.Methods:Fifty-one patients with Jocal advanced pancreatic cancer from June 2002 to February 2004 were enrolled.twenty-four patients of combined group were treared with transarterial infusion chemotherapy of gemcitabine plus three dimensional conformal radiotherapy.while twenty-seven patients of control group were treated only with transarterial infusion chemotherapy of gemcitabine.Results:There were significant statistical differences between two groupsin clinical benefil response(91.7%versus 74.1%,P<0.01)and overall remission rate(70.8%versus 33.3%,P<0.01).The 6-month survival rate,12-month survival rate and 24-month survival rate of combined group were 83.3%,62.5%and 37.5%respectively,while that of control group were 55.6%,33.3%and 11.1% respectively.This showed significant difierence between the two qroups.Conclusion:Transarterial infusion chemotherapy of gemcitabine plus three dimensional conformal radiotherapy may be better than single transarterial infusion chemotherapy of gemcitabine in improving survival rates and elongating survival time of patients with local advanced pancreatic cancer.

  17. Nanomedicine developments in the treatment of metastatic pancreatic cancer: focus on nanoliposomal irinotecan

    Directory of Open Access Journals (Sweden)

    Ko AH

    2016-03-01

    Full Text Available Andrew H KoDivision of Hematology/Oncology, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA Abstract: Nanoliposomal irinotecan (nal-IRI was originally developed using an efficient and high-loading capacity system to encapsulate irinotecan within a liposomal carrier, producing a therapeutic agent with improved biodistribution and pharmacokinetic characteristics compared to free drug. Specifically, administration of nal-IRI results in prolonged exposure of SN-38, the active metabolite of irinotecan, within tumors, while at the same time offering the advantage of less systemic toxicity than traditional irinotecan. These favorable properties of nal-IRI, confirmed in a variety of tumor xenograft models, led to its clinical evaluation in a number of disease indications for which camptothecins have proven activity, including in colorectal, gastric, and pancreatic cancers. The culmination of these clinical trials was the NAPOLI-1 (Nanoliposomal irinotecan with fluorouracil and folinic acid in metastatic pancreatic cancer after previous gemcitabine-based therapy trial, an international Phase III study evaluating nal-IRI both alone and in combination with 5-fluorouracil and leucovorin in patients with metastatic pancreatic adenocarcinoma following progression on gemcitabine-based chemotherapy. Positive results from NAPOLI-1 led to approval of nal-IRI (with 5-fluorouracil/leucovorin in October 2015 by the US Food and Drug Administration specifically for the treatment of metastatic pancreatic cancer in the second-line setting and beyond, a clinical context in which there had previously been no accepted standard of care. As such, nal-IRI represents an important landmark in cancer drug development, and potentially ushers in a new era where a greater number of patients with advanced pancreatic cancer can be sequenced through multiple lines of therapy translating into meaningful improvements in

  18. Developments in metastatic pancreatic cancer: Is gemcitabine still the standard?

    Institute of Scientific and Technical Information of China (English)

    Jie-Er Ying; Li-Ming Zhu; Bi-Xia Liu

    2012-01-01

    In the past 15 years,we have seen few therapeutic advances for patients with pancreatic cancer,which is the fourth leading cause of cancer-related death in the United States.Currently,only about 6% of patients with advanced disease respond to standard gemcitabine therapy,and median survival is only about 6 mo.Moreover,phase Ⅲ trials have shown that adding various cytotoxic and targeted chemotherapeutic agents to gemcitabine has failed to improve overall survival,except in cases in which gemcitabine combined with erlotinib show minimal survival benefit.Several metaanalyses have shown that the combination of gemcitabine with either a platinum analog or capecitabine may lead to clinically relevant survival prolongation,especially for patients with good performance status.Meanwhile,many studies have focused on the pharmacokinetic modulation of gemcitabine by fixed-dose administration,and metabolic or transport enzymes related to the response and toxicity of gemcitabine.Strikingly,a phase Ⅲ trial in 2010 showed that,in comparison to gemcitabine alone,the FOLFIRINOX regimen in patients with advanced disease and good performance status,produced better median overall survival,median progression-free survival,and objective response rates.This regimen also resulted in greater,albeit manageable toxicity.

  19. Anthropometric Measures, Body Mass Index and Pancreatic Cancer: a Pooled Analysis from the Pancreatic Cancer Cohort Consortium (PanScan)

    Science.gov (United States)

    Arslan, Alan A.; Helzlsouer, Kathy J.; Kooperberg, Charles; Shu, Xiao-Ou; Steplowski, Emily; Bueno-de-Mesquita, H. Bas; Fuchs, Charles S.; Gross, Myron D.; Jacobs, Eric J.; LaCroix, Andrea Z.; Petersen, Gloria M.; Stolzenberg-Solomon, Rachael Z.; Zheng, Wei; Albanes, Demetrius; Amundadottir, Laufey; Bamlet, William R.; Barricarte, Aurelio; Bingham, Sheila A.; Boeing, Heiner; Boutron-Ruault, Marie-Christine; Buring, Julie E.; Chanock, Stephen J.; Clipp, Sandra; Gaziano, J. Michael; Giovannucci, Edward L.; Hankinson, Susan E.; Hartge, Patricia; Hoover, Robert N.; Hunter, David J.; Hutchinson, Amy; Jacobs, Kevin B.; Kraft, Peter; Lynch, Shannon M.; Manjer, Jonas; Manson, JoAnn E.; McTiernan, Anne; McWilliams, Robert R.; Mendelsohn, Julie B.; Michaud, Dominique S.; Palli, Domenico; Rohan, Thomas E.; Slimani, Nadia; Thomas, Gilles; Tjønneland, Anne; Tobias, Geoffrey S.; Trichopoulos, Dimitrios; Virtamo, Jarmo; Wolpin, Brian M.; Yu, Kai; Zeleniuch-Jacquotte, Anne; Patel, Alpa V.

    2010-01-01

    Background Pooled data were analyzed from the NCI Pancreatic Cancer Cohort Consortium (PanScan) to study the association between pre-diagnostic anthropometric measures and risk of pancreatic cancer. Methods PanScan applied a nested case-control study design and included 2,170 cases and 2,209 controls. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using unconditional logistic regression for cohort-specific quartiles of body mass index (BMI), weight, height, waist circumference, and waist-to-hip ratio (WHR), as well as conventional BMI categories: underweight (<18.5 kg/m2), normal (18.5-24.9 kg/m2), overweight (25.0-29.9 kg/m2), obese (30.0-34.9 kg/m2), and severely obese (≥35.0 kg/m2). Models were adjusted for potential confounders. Results Among all subjects, a positive association between increasing BMI and risk of pancreatic cancer was observed (adjusted OR for the highest vs. lowest BMI quartile = 1.33, 95% CI = 1.12-1.58, Ptrend < 0.001). Among men, the adjusted OR for pancreatic cancer for the highest vs. lowest quartile of BMI was 1.33 (95% CI = 1.04-1.69, Ptrend <0.03). Among women, the adjusted OR for pancreatic cancer for the highest quartile of BMI was 1.34 (95% CI = 1.05-1.70, Ptrend = 0.01). Increased WHR was associated with increased risk of pancreatic cancer among women (adjusted OR for the highest vs. lowest quartile = 1.87, 95% CI = 1.31-2.69, Ptrend = 0.003) but less so in men. Conclusion The findings provide strong support for a positive association between BMI and pancreatic cancer risk. In addition, centralized fat distribution may increase pancreatic cancer risk, especially in women. PMID:20458087

  20. The Q705K and F359L Single-Nucleotide Polymorphisms of NOD-Like Receptor Signaling Pathway: Association with Chronic Pancreatitis, Pancreatic Cancer, and Periodontitis.

    Science.gov (United States)

    Miskiewicz, Andrzej; Szparecki, Grzegorz; Durlik, Marek; Rydzewska, Grażyna; Ziobrowski, Ireneusz; Górska, Renata

    2015-12-01

    The aim of this study was to establish the correlation between the occurrence of Q705K and F359L polymorphisms in patients diagnosed with pancreatic diseases and periodontal conditions of various degrees of severity. The above-mentioned genetic markers were assessed in patients with pancreatic cancer (n = 18) and chronic pancreatitis (n = 39) as well as in a healthy control group (n = 115). The established inclusion criteria were the following: Caucasian descent, non-smoking, and age range 20-80, with different levels of periodontitis activity according to S. Offenbacher's scale. The genotyping reactions were performed by means of an RT-PCR with the use of TaqMan(®) genotyping assay. Results of the study revealed that the state of periodontium was significantly worse in patients with chronic pancreatitis. The Q705K and F359L polymorphisms were associated with more advanced cases of periodontitis measured by clinical attachment level, whereas the Q705K was associated with intensified bleeding index. Furthermore, the F359L single-nucleotide polymorphism was significantly higher in the group with chronic pancreatitis (p periodontitis, pancreatic cancer, and chronic pancreatitis. These findings might constitute the basis for a new diagnostic and therapeutic approach.

  1. Synchronous gallbladder and pancreatic cancer associated with pancreaticobiliary maljunction.

    Science.gov (United States)

    Rungsakulkij, Narongsak; Boonsakan, Paisarn

    2014-10-21

    We report the case of a 46-year-old woman who presented with chronic intermittent abdominal pain without jaundice; abdominal ultrasonography showed thickening of the gallbladder wall and dilatation of the bile duct. Endoscopic retrograde cholangiopancreaticography showed pancreatobiliary maljunction with proximal common bile duct dilatation. Pancreatobiliary maljunction was diagnosed. A computed tomography scan of the abdomen showed suspected gallbladder cancer and distal common bile duct obstruction. A pancreatic head mass was incidentally found intraoperative. Radical cholecystectomy with pancreatoduodenectomy was performed. The pathological report showed gallbladder cancer that was synchronous with pancreatic head cancer. In the pancreatobiliary maljunction with pancreatobiliary reflux condition, double primary cancer of the pancreatobiliary system should be awared.

  2. Neural Regulation of Pancreatic Cancer: A Novel Target for Intervention

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Aeson [Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052 (Australia); Kim-Fuchs, Corina [Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052 (Australia); Department of Visceral Surgery and Medicine, University Hospital Bern, Bern 3010 (Switzerland); Le, Caroline P. [Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052 (Australia); Hollande, Frédéric [Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052 (Australia); Department of Pathology, University of Melbourne, Parkville 3010 (Australia); Sloan, Erica K., E-mail: erica.sloan@monash.edu [Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052 (Australia); Cousins Center for PNI, UCLA Semel Institute, Jonsson Comprehensive Cancer Center, and UCLA AIDS Institute, University of California Los Angeles, Los Angeles, CA 90095 (United States); Peter MacCallum Cancer Centre, Division of Cancer Surgery, East Melbourne, Victoria 3002 (Australia)

    2015-07-17

    The tumor microenvironment is known to play a pivotal role in driving cancer progression and governing response to therapy. This is of significance in pancreatic cancer where the unique pancreatic tumor microenvironment, characterized by its pronounced desmoplasia and fibrosis, drives early stages of tumor progression and dissemination, and contributes to its associated low survival rates. Several molecular factors that regulate interactions between pancreatic tumors and their surrounding stroma are beginning to be identified. Yet broader physiological factors that influence these interactions remain unclear. Here, we discuss a series of preclinical and mechanistic studies that highlight the important role chronic stress plays as a physiological regulator of neural-tumor interactions in driving the progression of pancreatic cancer. These studies propose several approaches to target stress signaling via the β-adrenergic signaling pathway in order to slow pancreatic tumor growth and metastasis. They also provide evidence to support the use of β-blockers as a novel therapeutic intervention to complement current clinical strategies to improve cancer outcome in patients with pancreatic cancer.

  3. miR-29c suppresses pancreatic cancer liver metastasis in an orthotopic implantation model in nude mice and affects survival in pancreatic cancer patients.

    Science.gov (United States)

    Zou, Yongkang; Li, Jianwei; Chen, Zhiyu; Li, Xiaowu; Zheng, Shuguo; Yi, Dong; Zhong, Ai; Chen, Jian

    2015-06-01

    We investigated mechanisms of pancreatic cancer metastasis and defined the biological role of miR-29c in pancreatic cancer metastasis. After two rounds of cell selection in vivo, pancreatic cancer cells with various metastatic potentials derived from spontaneous liver metastases were used as a model of pancreatic cancer to determine the role of miR-29c in pancreatic cancer metastasis. Pancreatic cancer samples were analyzed for miRNA-29c expression, and these levels were associated with survival between groups. miR-29c suppresses cell migration and invasion by targeting the MMP2 3'UTR. Overexpression of miR-29c suppresses pancreatic cancer liver metastasis in a nude mouse orthotopic implantation model. miR-29c expression was associated with metastasis and pancreatic cancer patient survival. miR-29c plays an important role in mediating pancreatic cancer metastasis to the liver by targeting MMP2. Therefore, miR-29c may serve as a novel marker of pancreatic cancer metastasis and possibly as a therapeutic target to treat pancreatic cancer liver metastasis.

  4. Treatment of pancreatic cancer with epidermal growth factor receptor-targeted therapy

    Directory of Open Access Journals (Sweden)

    Bryan A Faller

    2009-09-01

    Full Text Available Bryan A Faller, Barbara BurtnessDepartment of Medical Oncology, Fox Chase Cancer Center, Philadelphia, PA, USAAbstract: Pancreatic adenocarcinoma is a common malignancy that remains refractory to available therapies. Gemcitabine has long been the standard, first-line agent in advanced disease. The epidermal growth factor receptor (EGFR is a commonly expressed target in pancreatic cancer that is involved in tumor proliferation, metastasis, and induction of angiogenesis. The addition of the EGFR inhibitor erlotinib to gemcitabine has recently been demonstrated to provide a small, yet statistically significant, survival benefit in advanced disease. This has prompted further research into the applications of EGFR-targeted therapy in pancreatic cancer, albeit with disappointing results. Resistance to these therapies seems highly prevalent and has been implicated in their limited efficacy. The development of rash is associated with treatment efficacy and suggests that predictive factors may one day be identified to guide appropriate patient selection for these agents. Preclinical research has shown promise that resistance to EGFR-targeted therapies can be overcome through a variety of approaches. Application of this research in clinical trials may ultimately yield an unquestioned role for EGFR-targeted therapy in the management of this disease.Keywords: cetuximab, drug resistance, epidermal growth factor receptor, erlotinib, gemcitabine, pancreatic cancer

  5. Current opinion on lymphadenectomy in pancreatic cancer surgery

    Institute of Scientific and Technical Information of China (English)

    Theodoros E Pavlidis; Efstathios T Pavlidis; Athanasios K Sakantamis

    2011-01-01

    BACKGROUND: Adenocarcinoma of the pancreas exhibits aggressive behavior in growth, inducing an extremely poor prognosis with an overall median 5-year survival rate of only 1%-4%. Curative resection is the only potential therapeutic opportunity. DATA  SOURCES: A PubMed search of relevant articles published up to 2009 was performed to identify information about the value of lymphadenectomy and its extent in curative resection of pancreatic adenocarcinoma. RESULTS: Despite recent advances in chemotherapy, radio-therapy or even immunotherapy, surgery still remains the major factor that affects the outcome. The initial promising performance in Japan gave conflicting results in Western countries for the extended and more radical pancreatectomy;it has failed to prove beneficial. Four prospective, randomized trials on extended versus standard lymphadenectomy during pancreatic cancer surgery have shown no improvement in long-term survival by the extended resection. The exact lymph node status, including malignant spread and the total number retrieved as well as the lymph node ratio, is the most important prognostic factor. Positive lymph nodes after pancreatectomy are present in 70%. Paraaortic lymph node spread indicates poor prognosis. CONCLUSIONS: Undoubtedly, a standard lymphadenectomy including >15 lymph nodes must be no longer preferred in patients with the usual head location. The extended lymphadenectomy does not have any place, unless in randomized trials. In cases with body or tail location, the radical antegrade modular pancreatosplenectomy gives promising results. Nevertheless, accurate localization and detailed examination of the resected specimen are required for better staging.

  6. Changes of Th17/Treg cell and related cytokines in pancreatic cancer patients.

    Science.gov (United States)

    Wang, Xiaofang; Wang, Lei; Mo, Qingjiang; Dong, Yuqian; Wang, Guoqiang; Ji, Ankui

    2015-01-01

    To explore the mechanism of Th17 cells and Treg cells in the peripheral blood of patients with pancreatic cancer through analyzing the changes of the related genes and cytokines expression. 40 patients were divided into three groups based on clinical staging, and 20 healthy subjects were treated as normal control. Proportion of Th17 cells and Treg cells were detected by flow cytometry. RORα, RORγt, FoxP3, and CTLA-4 expression in peripheral blood mononuclear cells were detected by RT-PCR. IL-10, IL-23, INF-γ, TGF-β, and IL-17 cytokine levels in peripheral blood were determined by enzyme-linked immunosorbent assay (ELISA). The proportion of Th17 cells in peripheral blood of pancreatic cancer patients was lower than that in the normal control, while the proportion of Treg was higher. RORα and RORγt mRNA expression in Th17 cells from pancreatic cancer patients decreased, while FoxP3 and CTLA-4 mRNA expressions in Treg cells increased compared with the normal control. And the correlation analysis revealed that they were significantly correlated with clinical staging. Compared with healthy control, IL-23, IL-17 and INF-γ levels were lower in pancreatic cancer patients, while IL-10 and TGF-β levels were higher. Following the progression of disease, patients in advanced stage exhibited higher level of IL-10 and TGF-β, and lower levels of IL-23 and INF-γ. Pancreatic cancer patients exhibited Th17/Treg balance disorders with higher Treg and lower Th17 cells. They affect cytokine IL-10, IL-23, INF-γ, TGF-β, and IL-17 expression changes mainly through regulating transcription factors such as RORα, RORγt, FoxP3 and CTLA-4, suggesting that Th17/Treg balance disorders plays an important role in the tumorigenesis of pancreatic cancer.

  7. Dynamic contrast-enhanced CT in patients with pancreatic cancer

    DEFF Research Database (Denmark)

    Lauridsen, Carsten Ammitzbøl; Eriksen, Rie Østbjerg; Strauch, Louise Søborg;

    2016-01-01

    tissue, compared with measurements in pancreatic tissue outside of tumor, or normal pancreatic tissue in control groups of healthy volunteers. The studies were heterogeneous in the number of patients enrolled and scan protocols. Perfusion parameters measured and analyzed by DCE-CT might be useful......The aim of this systematic review is to provide an overview of the use of Dynamic contrast-enhanced Computed Tomography (DCE-CT) in patients with pancreatic cancer. This study was composed according to the PRISMA guidelines 2009. The literature search was conducted in PubMed, Cochrane Library...... in the investigation of characteristic vascular patterns of pancreatic exocrine tumors. Further clinical studies are desired for investigating the potential of DCE-CT in pancreatic tumors. Keywords:...

  8. Glufosfamide administered using a 1-hour infusion given as first-line treatment for advanced pancreatic cancer. A phase II trial of the EORTC-new drug development group.

    Science.gov (United States)

    Briasoulis, E; Pavlidis, N; Terret, C; Bauer, J; Fiedler, W; Schöffski, P; Raoul, J L; Hess, D; Selvais, R; Lacombe, D; Bachmann, P; Fumoleau, P

    2003-11-01

    The activity of glufosfamide (beta-D-glucopyranosyl-N,N'-di-(2-chloroethyl)-phosphoric acid diamide) against pancreatic cancer was investigated in a multicentre, phase II clinical study. Chemotherapy-nai;ve patients with advanced or metastatic disease were treated with glufosfamide (5 g/m(2)) using a 1-h intravenous (i.v.) infusion every 3 weeks. Patients were randomised between active-hydration and normal fluids to evaluate the nephroprotective effect of forced diuresis. Patients experiencing >0.4 mg/dl (>35 micromol/l) increase in serum creatinine compared with their baseline value were taken off treatment for safety reasons. The evaluation of response was according to the Response evaluation criteria in solid tumours (RECIST). Blood sampling was performed for pharmacokinetic analyses. 35 patients from 13 institutions were registered over a 13-month period. A total of 114 treatment cycles (median 3, range 1-8) were administered to 34 patients; 18 patients were allocated to the hydration arm. Overall haematological toxicity was mild. Metabolic acidosis occurred in 2 patients treated in the active-hydration arm, grade 3 hypokalaemia was recorded in 5 patients and grade 3 hypophosphataemia in 4 patients. One patient had a grade 4 increase in serum creatinine level, concomitantly to disease progression. Active-hydration did not show a nephroprotective effect and the plasma pharmacokinetics (Pk) of glufosfamide was not significantly influenced by hydration. Two confirmed partial remissions (PR) were reported (response rate 5.9%, 95% Confidence Interval (CI) 0.7-19.7%) and 11 cases obtained disease stabilisation (32.4%). An extra mural review panel confirmed all of the responses. Median overall survival was 5.3 months (95% CI 3.9-7.1) and time to progression (TTP) was 1.4 months (95% CI 1.3-2.7). In conclusion, glufosfamide administered using a 1-h infusion every 3 weeks has a modest activity in advanced pancreatic adenocarcinoma. Haematological toxicity is

  9. A mathematical prognosis model for pancreatic cancer patients receiving immunotherapy.

    Science.gov (United States)

    Li, Xuefang; Xu, Jian-Xin

    2016-10-07

    Pancreatic cancer is one of the most deadly types of cancer since it typically spreads rapidly and can seldom be detected in its early stage. Pancreatic cancer therapy is thus a challenging task, and appropriate prognosis or assessment for pancreatic cancer therapy is of critical importance. In this work, based on available clinical data in Niu et al. (2013) we develop a mathematical prognosis model that can predict the overall survival of pancreatic cancer patients who receive immunotherapy. The mathematical model incorporates pancreatic cancer cells, pancreatic stellate cells, three major classes of immune effector cells CD8+ T cells, natural killer cells, helper T cells, and two major classes of cytokines interleukin-2 (IL-2) and interferon-γ (IFN-γ). The proposed model describes the dynamic interaction between tumor and immune cells. In order for the model to be able to generate appropriate prognostic results for disease progression, the distribution and stability properties of equilibria in the mathematical model are computed and analysed in absence of treatments. In addition, numerical simulations for disease progression with or without treatments are performed. It turns out that the median overall survival associated with CIK immunotherapy is prolonged from 7 to 13months compared with the survival without treatment, this is consistent with the clinical data observed in Niu et al. (2013). The validity of the proposed mathematical prognosis model is thus verified. Our study confirms that immunotherapy offers a better prognosis for pancreatic cancer patients. As a direct extension of this work, various new therapy methods that are under exploration and clinical trials could be assessed or evaluated using the newly developed mathematical prognosis model.

  10. Pancreatic cancer mortality in China (1991-2000)

    Institute of Scientific and Technical Information of China (English)

    Li Wang; Gong-Huan Yang; Xing-Hua Lu; Zheng-Jing Huang; Hui Li

    2003-01-01

    AIM: To describe the mortality rate of pancreatic cancer and its distribution in China during the period of 1991-2000.METHODS: Based on the data of demography and death collected through China′s Disease Surveillance Point System (DSPS) over the period of 1991-2000, the distribution of death rate of pancreatic cancer was described in terms of age group, gender, calendar year, rural/urban residence and administrative district.RESULTS: A total of 1 619 death cases attributed to pancreatic cancer (975 men and 644 women) were reported by DSPS during 1991-2000. The reported, adjusted and agestandardized mortality rates increased from 1.46, 1.75, and 2.18 per 100 000 populations in 1991 to 2.38, 3.06, and 3.26per 100 000 populations in 2000. The majority (69.62 %) of the deaths of pancreatic cancer were seen in the age group of 60 years and older. The mortality rate was higher in men than in women, but the male to female death rate ratios decreased during the 10 years. Our data also showed that the death rate of pancreatic cancer in urban areas was about 2-4 fold higher than that in rural areas, and in Northeast and East China, the death rates were higher than those in the other 5 administrative districts.CONCLUSION: The death rate due to pancreatic cancer was rising during the period of 1991-2000 and the peak mortality of pancreatic cancer might arrive in China.

  11. Cadmium Exposure and Pancreatic Cancer in South Louisiana

    Directory of Open Access Journals (Sweden)

    Brian G. Luckett

    2012-01-01

    Full Text Available Cadmium has been hypothesized to be a pancreatic carcinogen. We test the hypothesis that cadmium exposure is a risk factor for pancreatic cancer with a population-based case-control study sampled from a population with persistently high rates of pancreatic cancer (south Louisiana. We tested potential dietary and nondietary sources of cadmium for their association with urinary cadmium concentrations which reflect long-term exposure to cadmium due to the accumulation of cadmium in the kidney cortex. Increasing urinary cadmium concentrations were significantly associated with an increasing risk of pancreatic cancer (2nd quartile OR = 3.34, 3rd = 5.58, 4th = 7.70; test for trend P≤0.0001. Potential sources of cadmium exposure, as documented in the scientific literature, found to be statistically significantly associated with increased risk of pancreatic cancer included working as a plumber, pipefitter or welder (OR = 5.88 and high consumption levels of red meat (4th quartile OR = 6.18 and grains (4th quartile OR = 3.38. Current cigarette smoking, at least 80 pack years of smoking, occupational exposure to cadmium and paints, working in a shipyard, and high consumption of grains were found to be statistically significantly associated with increased concentrations of urinary cadmium. This study provides epidemiologic evidence that cadmium is a potential human pancreatic carcinogen.

  12. Developing a multicenter cooperative research system for pancreatic cancer in China

    Institute of Scientific and Technical Information of China (English)

    ZHAO Yu-pei

    2007-01-01

    @@ Pancreatic cancer often starts silently without symptoms at its early stage but progresses quite rapidly and has a poor prognosis. In recent years the incidence of pancreatic cancer has been rising year by year.1

  13. Physical activity, energy restriction, and the risk of pancreatic cancer: Prospective study in the Netherlands

    NARCIS (Netherlands)

    Heinen, M.M.; Verhage, B.A.J.; Goldbohm, R.A.; Lumey, L.H.; Brandt, P.A. van den

    2011-01-01

    Background: Because of their influence on insulin concentrations, we hypothesized that both physical activity and energy restriction may reduce the risk of pancreatic cancer. Objective: We examined the associations between physical activity, proxies for energy restriction, and pancreatic cancer risk

  14. Adenylate cyclase-associated protein 1 overexpressed in pancreatic cancers is involved in cancer cell motility.

    Science.gov (United States)

    Yamazaki, Ken; Takamura, Masaaki; Masugi, Yohei; Mori, Taisuke; Du, Wenlin; Hibi, Taizo; Hiraoka, Nobuyoshi; Ohta, Tsutomu; Ohki, Misao; Hirohashi, Setsuo; Sakamoto, Michiie

    2009-04-01

    Pancreatic cancer has the worst prognosis among cancers due to the difficulty of early diagnosis and its aggressive behavior. To characterize the aggressiveness of pancreatic cancers on gene expression, pancreatic cancer xenografts transplanted into severe combined immunodeficient mice served as a panel for gene-expression profiling. As a result of profiling, the adenylate cyclase-associated protein 1 (CAP1) gene was shown to be overexpressed in all of the xenografts. The expression of CAP1 protein in all 73 cases of pancreatic cancer was recognized by immunohistochemical analyses. The ratio of CAP1-positive tumor cells in clinical specimens was correlated with the presence of lymph node metastasis and neural invasion, and also with the poor prognosis of patients. Immunocytochemical analyses in pancreatic cancer cells demonstrated that CAP1 colocalized to the leading edge of lamellipodia with actin. Knockdown of CAP1 by RNA interference resulted in the reduction of lamellipodium formation, motility, and invasion of pancreatic cancer cells. This is the first report demonstrating the overexpression of CAP1 in pancreatic cancers and suggesting the involvement of CAP1 in the aggressive behavior of pancreatic cancer cells.

  15. Methods and Rationale for the Early Detection of Pancreatic Cancer Highlights from the "2010 ASCO Gastrointestinal Cancers Symposium". Orlando, FL, USA. January 22-24, 2010

    Directory of Open Access Journals (Sweden)

    Scott Bussom

    2010-03-01

    Full Text Available Pancreatic cancer often presents at an advanced stage that result in a very dismal five-year survival rates. Novel methods to detect tumors as early as possible are desperately needed. The U.S. Preventive Services Task Force (USPSTF recommends against routine screening for pancreatic cancer in asymptomatic adults using abdominal palpation, ultrasonography, or serologic markers. The evidence for diet-based prevention of pancreatic cancer is limited and conflicting. Recommendations about lifestyle changes, such as stopping the use of tobacco products, moderating alcohol intake, and eating a balanced diet with sufficient fruit and vegetables is generally made. However, screening for persons with hereditary predisposition to develop pancreatic cancer has not been included in this review. Biomarkers represent one tool for the early detection of small, surgically resectable cancers in both the general and high risk populations. Some of the currently utilized biomarkers including carcinoembryonic antigen (CEA, CA 19-9, SPan-1, and DUPAN-2 unfortunately have yet to show the sensitivity and specificity needed to be used for screening asymptomatic patients in the general population for pancreatic cancer. Herein, the authors report some updated information from the 2010 ASCO Gastrointestinal Cancers Symposium in detecting early stage pancreatic cancer.

  16. Strategy to differentiate autoimmune pancreatitis from pancreas cancer

    Institute of Scientific and Technical Information of China (English)

    Kensuke Takuma; Terumi Kamisawa; Rajesh Gopalakrishna; Seiichi Hara; Taku Tabata; Yoshihiko Inaba; Naoto Egawa

    2012-01-01

    Autoimmune pancreatitis (AIP) is a newly described entity of pancreatitis in which the pathogenesis appears to involve autoimmune mechanisms.Based on histological and immunohistochemical examinations of various organs of AIP patients,AIP appears to be a pancreatic lesion reflecting a systemic "IgG4-related sclerosing disease".Clinically,AIP patients and patients with pancreatic cancer share many features,such as preponderance of elderly males,frequent initial symptom of painless jaundice,development of new-onset diabetes mellitus,and elevated levels of serum tumor markers.It is of uppermost importance not to misdiagnose AIP as pancreatic cancer.Since there is currently no diagnostic serological marker for AIP,and approach to the pancreas for histological examination is generally difficult,AIP is diagnosed using a combination of clinical,serological,morphological,and histopathological features.Findings suggesting AIP rather than pancreatic cancer include:fluctuating obstructive jaundice; elevated serum IgG4 levels; diffuse enlargement of the pancreas; delayed enhancement of the enlarged pancreas and presence of a capsule-like rim on dynamic computed tomography; low apparent diffusion coefficient values on diffusion-weighted magnetic resonance image; irregular narrowing of the main pancreatic duct on endoscopic retrograde cholangiopancreatography; less upstream dilatation of the main pancreatic duct on magnetic resonance cholangiopancreatography,presence of other organ involvement such as bilateral salivary gland swelling,retroperitoneal fibrosis and hilar or intrahepatic sclerosing cholangitis;negative work-up for malignancy including endoscopic ultrasound-guided fine needle aspiration; and steroid responsiveness.Since AIP responds dramatically to steroid therapy,accurate diagnosis of AIP can avoid unnecessary laparotomy or pancreatic resection.

  17. Prognostic value of PDL1 expression in pancreatic cancer.

    Science.gov (United States)

    Birnbaum, David J; Finetti, Pascal; Lopresti, Alexia; Gilabert, Marine; Poizat, Flora; Turrini, Olivier; Raoul, Jean-Luc; Delpero, Jean-Robert; Moutardier, Vincent; Birnbaum, Daniel; Mamessier, Emilie; Bertucci, François

    2016-11-01

    Pancreatic cancer is one of the most aggressive human cancers. PD1/PDL1-inhibitors recently showed promising results in different cancers with correlation between PDL1 tumor expression and responses. Expression of programmed cell death receptor ligand 1 (PDL1) has been scarcely studied in pancreatic cancer. In this retrospective study, we analyzed PDL1 mRNA expression in 453 clinical pancreatic cancer samples profiled using DNA microarrays and RNASeq. Compared to normal pancreatic samples, PDL1 expression was upregulated in 19% of cancer samples. Upregulation was not associated with clinicopathological features such as patients' age and sex, pathological type, tumor size, lymph node status, and grade, but was associated with shorter disease-free survival and overall survival in multivariate analyses. Analysis of correlations with biological parameters showed that PDL1 upregulation was associated with some degree of lymphocyte infiltration and signs of anti-tumor T-cell response, but to a lesser extent than what has been reported in breast cancer and GIST. PDL1-up pancreatic cancers displayed profiles of lymphocyte exhaustion, were more enriched in inhibitory molecules and pro-tumor populations (Tregs with upregulation of FOXP3 and IL10, myeloid-derived suppressor cells with upregulation of CD33 and S100A8/A9), and demonstrated a down-modulation of most MHC class I members (HLA-A/B/C, HLA-E/F/G) suggestive of a defect in antigen processing and presentation. In conclusion, our results suggest that PDL1 expression might refine the prediction of metastatic relapse in operated pancreatic cancer, and that PD1/PDL1 inhibitors might reactivate inhibited T-cells to increase the anti-tumor immune response in PDL1-upregulated tumors.

  18. STAT3 as an emerging molecular target in pancreatic cancer

    Directory of Open Access Journals (Sweden)

    Sharma NK

    2014-08-01

    Full Text Available Narinder Kumar Sharma,1 Sharmila Shankar,2 Rakesh K Srivastava1 1Department of Pharmacology, Toxicology and Therapeutics, and Medicine, University of Kansas Medical Center, Kansas City, KS, USA; 2Kansas City VA Medical Center, Kansas City, MO, USA Abstract: Pancreatic cancer is the fourth leading cause of cancer related deaths. Although, surgical resection of pancreatic cancer may provide the best chance for cure and long-term survival, due to the late onset of symptoms only 15% to 20% of patients have resectable tumors. Most of the pancreatic tumors have mutations in the K-ras gene, followed by mutations in tumor suppressor genes such as p53 and SMAD4. In addition, there is growing evidence for the potential involvement of signal transducer and activator of transcription 3 (STAT3 in malignant transformation of pancreatic cancer. STAT3 plays critical roles in regulating many physiological functions in normal and malignant tissues, such as inflammation, survival, proliferation, differentiation, and angiogenesis. STAT3 is activated by a wide variety of cytokines, growth factors, and other stimuli. Unlike other members of the STAT family, ablation of STAT3 leads to embryonic lethality and conditional loss of STAT3 protein in adult tissues, leading to a variety of abnormalities, confirming that STAT3 participates in a wide variety of physiological processes. Constitutive activation of STAT3 is implicated in a wide range of human cancers; therefore, STAT3 has been identified as a novel target to treat and prevent cancers. Several STAT3 inhibitors display antitumor effectiveness, and data supporting the use of STAT3 inhibitors are emerging. Different approaches used for the inhibition of activated STAT3 include modulating upstream positive or negative regulators or directly targeting its different domains. These approaches have been used in the inhibition of STAT3 in different cancers, but in this review, we will focus specifically on the inhibition

  19. Palliative Care in Improving Quality of Life and Symptoms in Patients With Stage III-IV Pancreatic or Ovarian Cancer

    Science.gov (United States)

    2014-12-18

    Recurrent Ovarian Epithelial Cancer; Recurrent Ovarian Germ Cell Tumor; Recurrent Pancreatic Cancer; Stage III Pancreatic Cancer; Stage IIIA Ovarian Epithelial Cancer; Stage IIIA Ovarian Germ Cell Tumor; Stage IIIB Ovarian Epithelial Cancer; Stage IIIB Ovarian Germ Cell Tumor; Stage IIIC Ovarian Epithelial Cancer; Stage IIIC Ovarian Germ Cell Tumor; Stage IV Ovarian Epithelial Cancer; Stage IV Ovarian Germ Cell Tumor; Stage IV Pancreatic Cancer

  20. Multivisceral Resection For Pancreatic Head Cancer: Is It Worthwhile?

    Directory of Open Access Journals (Sweden)

    Jose Manuel Ramia-Ange

    2016-07-01

    Full Text Available Pancreatic cancer has a dismal prognosis [1, 2]. Surgical resection with negative margins is the best treatment option and the only curative one, but it obtains a 5-year survival rate of only 15-25% [1, 2, 3]. When the tumor is located in the pancreatic head, pancreaticoduodenectomy (PD is performed. This surgical technique includes the resection of several organs (pancreatic head, duodenum, bile duct, gallbladder and distal stomach [1, 4]. At specialized centers, PD presents a postoperative mortality rate of 5% and a morbidity rate of around 50% [1, 2, 4].

  1. Road map for pain management in pancreatic cancer: A review

    Institute of Scientific and Technical Information of China (English)

    Marie José Lahoud; Hampig Raphael Kourie; Joelle Antoun; Lana El Osta; Marwan Ghosn

    2016-01-01

    Beside its poor prognosis and its late diagnosis, pancreatic cancer remains one of the most painful malignancies. Optimal management of pain in this cancer represents a real challenge for the oncologist whose objective is to ensure a better quality of life to his patients. We aimed in this paper to review all the treatment modalities incriminated in the management of pain in pancreatic cancer going from painkillers, chemotherapy, radiation therapy and interventional techniques to agents under investigation and alternative medicine. Although specific guidelines and recommendations for pain management in pancreatic cancer are still absent, we present all the possible pain treatments, with a progression from medical multimodal treatment to radiotherapy and chemotherapy then interventional techniques in case of resistance. In addition, alternative methods such as acupuncture and hypnosis can be added at any stage and seems to contribute to pain relief.

  2. Expression profiling identifies microRNA signature in pancreatic cancer

    OpenAIRE

    Lee, Eun Joo; Gusev, Yuriy; Jiang, Jinmai; Gerard J Nuovo; Lerner, Megan R; Frankel, Wendy L.; Morgan, Daniel L.; Postier, Russell G.; Brackett, Daniel J; Schmittgen, Thomas D.

    2007-01-01

    microRNAs are functional, 22 nt, noncoding RNAs that negatively regulate gene expression. Disturbance of microRNA expression may play a role in the initiation and progression of certain diseases. A microRNA expression signature has been identified that is associated with pancreatic cancer. This has been accomplished with the application of real-time PCR profiling of over 200 microRNA precursors on specimens of human pancreatic adenocarcinoma, paired benign tissue, normal pancreas, chronic pan...

  3. Contrast-enhanced endoscopic ultrasound in discrimination between focal pancreatitis and pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    Michael Hocke; Ewald Schulze; Peter Gottschalk; Theodor Topalidis; Christoph F Dietrich

    2006-01-01

    AIM: To evaluate the contrast-enhanced endosonography as a method of differentiating inflammation from pancreatic carcinoma based on perfusion characteristics of microvessels.METHODS: In 86 patients with suspected chronic pancreatitis (age: 62±12 years; sex: f/m 38/48), pancreatic lesions were examined by conventional endoscopic B-mode, power Doppler ultrasound and contrastenhanced power mode (Hitachi EUB 525, SonoVue(R), 2.4mL, Bracco) using the following criteria for malignant lesions: no detectable vascularisation using conventional power Doppler scanning, irregular appearance of arterial vessels over a short distance using SonoVue(R) contrastenhanced technique and no detectable venous vessels inside the lesion. A malignant lesion was assumed if all criteria were detectable [gold standard endoscopic ultrasound (EUS)-guided fine needle aspiration cytology,operation]. The criteria of chronic pancreatitis without neoplasia were defined as no detectable vascularisation before injection of SonoVue(R), regular appearance of vessels over a distance of at least 20 mm after injection of SonoVue(R) and detection of arterial and venous vessels.RESULTS: The sensitivity and specificity of conventional EUS were 73.2% and 83.3% respectively for pancreatic cancer. The sensitivity of contrast-enhanced EUS increased to 91.1% in 51 of 56 patients with malignant pancreatic lesion and the specificity increased to 93.3%in 28 of 30 patients with chronic inflammatory pancreatic disease.CONCLUSION: Contrast-enhanced endoscopic ultrasound improves the differentiation between chronic pancreatitis and pancreatic carcinoma.

  4. Targeting tumor tolerance: A new hope for pancreatic cancer therapy?

    Science.gov (United States)

    Delitto, Daniel; Wallet, Shannon M; Hughes, Steven J

    2016-10-01

    With a 5-year survival rate of just 8%, pancreatic cancer (PC) is projected to be the second leading cause of cancer deaths by 2030. Most PC patients are not eligible for surgery with curative intent upon diagnosis, emphasizing a need for more effective therapies. However, PC is notoriously resistant to chemoradiation regimens. As an alternative, immune modulating strategies have recently achieved success in melanoma, prompting their application to other solid tumors. For such therapeutic approaches to succeed, a state of immunologic tolerance must be reversed in the tumor microenvironment and that has been especially challenging in PC. Nonetheless, knowledge of the PC immune microenvironment has advanced considerably over the past decade, yielding new insights and perspectives to guide multimodal therapies. In this review, we catalog the historical groundwork and discuss the evolution of the cancer immunology field to its present state with a specific focus on PC. Strategies currently employing immune modulation in PC are reviewed, specifically highlighting 66 clinical trials across the United States and Europe.

  5. 胰腺癌综合治疗的现状%Current status of the combined therapy for pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    倪泉兴; 李骥

    2009-01-01

    Pancreatic cancer is one of the worst digestive malignancies characterized by non-specific symptoms, rapid progression and high mortality. Despite great efforts that have been made in basic and clinical research, the prognosis remains poor with an overall 5-year survival rate of less than 5%. Complete surgical resection is the only curative treatment option, but the curative resectabillty is still about 15% in China. Pancreatic surgery is considered one of the most techni-cally demanding and challenging procedures. The development of pancreatic surgery in China depends not only on the progress in surgical techniques, but also the specialization on pancreatic surgery. There has been advancement in combined therapy with a modern interdisciplinary approach including chemotherapy,radiotherapy, biotherapy and thermotherapy. The research pro-gress of gene therapy on pancreatic cancer showed us some hopes for the future. The outcome of pancreatic cancer treated by Chinese medicine with herbal drugs is encouraging, but still needs the support of more solid evidences from randomized con-trolled trials. It is suggested that the combined therapy should play an important role in the treatment of pancreatic cancer, and the fallow-up should be paid more attention.

  6. The Genetics and Molecular Alterations of Pancreatic Cancer

    NARCIS (Netherlands)

    Wilde, R.F. de

    2015-01-01

    The prospect that pancreatic cancer will be the second most common cause of cancer death by 2030 is worrisome. Considering that the approximate 6% overall 5-year survival has not merely changed in the past decades illustrates the need to revert the bleak prognosis. Centralization of surgery (pancr

  7. Fascin promotes the motility and invasiveness of pancreatic cancer cells

    Institute of Scientific and Technical Information of China (English)

    Yan-Feng Xu; Shuang-Ni Yu; Zhao-Hui Lu; Jian-Ping Liu; Jie Chen

    2011-01-01

    AIM: To explore the role of actin-bundling protein, fascin during the progression of pancreatic cancer. METHODS: The plasmid expressing human fascin-1 was stably transfected into the pancreatic cancer cell line MIA PaCa-2. The proliferation, cell cycle, motility, scattering, invasiveness and organization of the actin filament system in fascin-transfected MIA PaCa-2 cells and control non-transfected cells were determined. RESULTS: Heterogeneous overexpression of fascin markedly enhanced the motility, scattering, and invasiveness of MIA PaCa-2 cells. However, overexpression of fascin had minimal effect on MIA PaCa-2 cell proliferation and cell cycle. In addition, cell morphology and organization of the actin filament system were distinctly altered in fascin overexpressed cells. When transplanted into BALB/c-nu mice, fascin-transfected pancreatic cancer cells developed solid tumors at a slightly slower rate, but these tumors displayed more aggressive behavior in comparison with control tumors. CONCLUSION: Fascin promotes pancreatic cancer cell migration, invasion and scattering, thus contributes to the aggressive behavior of pancreatic cancer cells.

  8. Survivin expression and its clinical significance in pancreatic cancer

    Directory of Open Access Journals (Sweden)

    Lee Kyung Shik

    2005-10-01

    Full Text Available Abstract Background Survivin, an inhibitor of apoptosis is expressed in several human cancers. Its expression is known to be associated with poor clinical outcome, but not widely studied in pancreatic cancer. We performed this study to determine the survivin expression in pancreatic cancer and its clinical significance as a prognostic factor. Methods We performed immunohistochemical staining for survivin, p53, and Bax in formalin-fixed, paraffin-embedded block from forty-nine pancreatic tissues. To determine the association with clinical course, we reviewed the patients' clinical record. Results Of the 49 cases of pancreatic cancer, 46 cases (93.9% were positive for survivin expression. There was no significant association between survivin expression and p53 or bax. For clinicopathological parameters, perineural invasion was more common in survivin positive and venous invasion was more common in survivin negative (p = 0.041 and 0.040, respectively. Responsiveness to chemotherapy appeared to be slightly better in patients with low survivin expression. Conclusion Survivin expression may be associated with venous or perineural invasion, indicating metastatic route, and seems to have a potential as a predictive marker for chemotherapy. Further study of large scale is required to determine the clinical significance of survivin expression in pancreatic cancer.

  9. MicroRNA biomarkers in whole blood for detection of pancreatic cancer

    DEFF Research Database (Denmark)

    Schultz, Nicolai A; Dehlendorff, Christian; Jensen, Benny V

    2014-01-01

    IMPORTANCE: Biomarkers for the early diagnosis of patients with pancreatic cancer are needed to improve prognosis. OBJECTIVES: To describe differences in microRNA expression in whole blood between patients with pancreatic cancer, chronic pancreatitis, and healthy participants and to identify panels...... of microRNAs for use in diagnosis of pancreatic cancer compared with the cancer antigen 19-9 (CA19-9). DESIGN, SETTING, AND PARTICIPANTS: A case-control study that included 409 patients with pancreatic cancer and 25 with chronic pancreatitis who had been included prospectively in the Danish BIOPAC...... (Biomarkers in Patients with Pancreatic Cancer) study (July 2008-October 2012) plus 312 blood donors as healthy participants. The microRNA expressions in pretreatment whole blood RNA samples were collected and analyzed in 3 randomly determined subcohorts: discovery cohort (143 patients with pancreatic cancer...

  10. The Notch pathway is important in maintaining the cancer stem cell population in pancreatic cancer.

    Directory of Open Access Journals (Sweden)

    Ethan V Abel

    Full Text Available Pancreatic cancer stem cells (CSCs represent a small subpopulation of pancreatic cancer cells that have the capacity to initiate and propagate tumor formation. However, the mechanisms by which pancreatic CSCs are maintained are not well understood or characterized.Expression of Notch receptors, ligands, and Notch signaling target genes was quantitated in the CSC and non-CSC populations from 8 primary human pancreatic xenografts. A gamma secretase inhibitor (GSI that inhibits the Notch pathway and a shRNA targeting the Notch target gene Hes1 were used to assess the role of the Notch pathway in CSC population maintenance and pancreatic tumor growth.Notch pathway components were found to be upregulated in pancreatic CSCs. Inhibition of the Notch pathway using either a gamma secretase inhibitor or Hes1 shRNA in pancreatic cancer cells reduced the percentage of CSCs and tumorsphere formation. Conversely, activation of the Notch pathway with an exogenous Notch peptide ligand increased the percentage of CSCs as well as tumorsphere formation. In vivo treatment of orthotopic pancreatic tumors in NOD/SCID mice with GSI blocked tumor growth and reduced the CSC population.The Notch signaling pathway is important in maintaining the pancreatic CSC population and is a potential therapeutic target in pancreatic cancer.

  11. File list: Unc.Pan.20.AllAg.Pancreatic_cancer_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Pan.20.AllAg.Pancreatic_cancer_cells mm9 Unclassified Pancreas Pancreatic cancer... cells http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Unc.Pan.20.AllAg.Pancreatic_cancer_cells.bed ...

  12. File list: ALL.Pan.10.AllAg.Pancreatic_cancer_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Pan.10.AllAg.Pancreatic_cancer_cells mm9 All antigens Pancreas Pancreatic cancer... cells SRX174586,SRX174585,SRX174587 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/ALL.Pan.10.AllAg.Pancreatic_cancer_cells.bed ...

  13. File list: Oth.Pan.10.AllAg.Pancreatic_cancer_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Pan.10.AllAg.Pancreatic_cancer_cells mm9 TFs and others Pancreas Pancreatic cancer... cells SRX174586,SRX174585 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Pan.10.AllAg.Pancreatic_cancer_cells.bed ...

  14. File list: Pol.Pan.20.AllAg.Pancreatic_cancer_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Pan.20.AllAg.Pancreatic_cancer_cells mm9 RNA polymerase Pancreas Pancreatic cancer... cells http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Pan.20.AllAg.Pancreatic_cancer_cells.bed ...

  15. Decision making in the treatment of pancreatic cancer : a retrospective analysis

    NARCIS (Netherlands)

    J.H.G. Klinkenbijl (Jean)

    1994-01-01

    textabstractPancreatic cancer is a major and often frustrating disease in clinical gastroenterology. Diagnosis and treatment are very difficult; 90% of all patients diagnosed with pancreatic cancer die within one year after diagnosis has been made. The incidence of pancreatic cancer has increased st

  16. File list: DNS.Pan.20.AllAg.Pancreatic_cancer_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available DNS.Pan.20.AllAg.Pancreatic_cancer_cells mm9 DNase-seq Pancreas Pancreatic cancer c...ells http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/DNS.Pan.20.AllAg.Pancreatic_cancer_cells.bed ...

  17. File list: ALL.Pan.05.AllAg.Pancreatic_cancer_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Pan.05.AllAg.Pancreatic_cancer_cells mm9 All antigens Pancreas Pancreatic cance...r cells SRX174586,SRX174585,SRX174587 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/ALL.Pan.05.AllAg.Pancreatic_cancer_cells.bed ...

  18. File list: Pol.Pan.50.AllAg.Pancreatic_cancer_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Pan.50.AllAg.Pancreatic_cancer_cells mm9 RNA polymerase Pancreas Pancreatic can...cer cells http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Pan.50.AllAg.Pancreatic_cancer_cells.bed ...

  19. File list: Unc.Pan.50.AllAg.Pancreatic_cancer_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Pan.50.AllAg.Pancreatic_cancer_cells mm9 Unclassified Pancreas Pancreatic cance...r cells http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Unc.Pan.50.AllAg.Pancreatic_cancer_cells.bed ...

  20. File list: ALL.Pan.50.AllAg.Pancreatic_cancer_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Pan.50.AllAg.Pancreatic_cancer_cells mm9 All antigens Pancreas Pancreatic cance...r cells SRX174585,SRX174586,SRX174587 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/ALL.Pan.50.AllAg.Pancreatic_cancer_cells.bed ...

  1. File list: His.Pan.05.AllAg.Pancreatic_cancer_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Pan.05.AllAg.Pancreatic_cancer_cells mm9 Histone Pancreas Pancreatic cancer cel...ls http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Pan.05.AllAg.Pancreatic_cancer_cells.bed ...

  2. File list: Oth.Pan.20.AllAg.Pancreatic_cancer_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Pan.20.AllAg.Pancreatic_cancer_cells mm9 TFs and others Pancreas Pancreatic can...cer cells SRX174585,SRX174586 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Pan.20.AllAg.Pancreatic_cancer_cells.bed ...

  3. Study on the biological characteristics of pancreatic cancer vascular endothelial cells

    Institute of Scientific and Technical Information of China (English)

    李雷

    2012-01-01

    Objective To explore the biological characteristics of pancreatic cancer vascular endothelial cells,including the aspects of morphology,species,genetics,vascular formation ability,and proliferation ability in vitro. Methods The human pancreatic cancer cells were inoculated in nude mice pancreas to get pancreatic cancer

  4. File list: Oth.Pan.05.AllAg.Pancreatic_cancer_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Pan.05.AllAg.Pancreatic_cancer_cells mm9 TFs and others Pancreas Pancreatic cancer... cells SRX174586,SRX174585 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Pan.05.AllAg.Pancreatic_cancer_cells.bed ...

  5. Diffusion-weighted imaging of pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    Riccardo; De; Robertis; Paolo; Tinazzi; Martini; Emanuele; Demozzi; Flavia; Dal; Corso; Claudio; Bassi; Paolo; Pederzoli; Mirko; D’Onofrio

    2015-01-01

    Magnetic resonance imaging(MRI) is a reliable and accurate imaging method for the evaluation of patients with pancreatic ductal adenocarcinoma(PDAC). Diffusion-weighted imaging(DWI) is a relatively recent technological improvement that expanded MRI capabilities, having brought functional aspects into conventional morphologic MRI evaluation. DWI can depict the random diffusion of water molecules within tissues(the so-called Brownian motions). Modifications of water diffusion induced by different factors acting on the extracellular and intracellular spaces, as increased cell density, edema, fibrosis, or altered functionality of cell membranes, can be detected using this MR sequence. The intravoxel incoherent motion(IVIM) model is an advanced DWI technique that consent a separate quantitative evaluation of all the microscopic random motions that contribute to DWI, which are essentially represented by molecular diffusion and blood microcirculation(perfusion). Technological improvements have made possible the routine use of DWI during abdominal MRI study. Several authors have reported that the addition of DWI sequence can be of value for the evaluation of patients with PDAC, especially improving the staging; nevertheless, it is still unclear whether and how DWI could be helpful for identification, characterization, prognostic stratification and follow-up during treatment. The aim of this paper is to review up-to-date literature data regarding the applications of DWI and IVIM to PDACs.

  6. TGF-β Blockade Reduces Mortality and Metabolic Changes in a Validated Murine Model of Pancreatic Cancer Cachexia.

    Directory of Open Access Journals (Sweden)

    Stephanie H Greco

    Full Text Available Cancer cachexia is a debilitating condition characterized by a combination of anorexia, muscle wasting, weight loss, and malnutrition. This condition affects an overwhelming majority of patients with pancreatic cancer and is a primary cause of cancer-related death. However, few, if any, effective therapies exist for both treatment and prevention of this syndrome. In order to develop novel therapeutic strategies for pancreatic cancer cachexia, appropriate animal models are necessary. In this study, we developed and validated a syngeneic, metastatic, murine model of pancreatic cancer cachexia. Using our model, we investigated the ability of transforming growth factor beta (TGF-β blockade to mitigate the metabolic changes associated with cachexia. We found that TGF-β inhibition using the anti-TGF-β antibody 1D11.16.8 significantly improved overall mortality, weight loss, fat mass, lean body mass, bone mineral density, and skeletal muscle proteolysis in mice harboring advanced pancreatic cancer. Other immunotherapeutic strategies we employed were not effective. Collectively, we validated a simplified but useful model of pancreatic cancer cachexia to investigate immunologic treatment strategies. In addition, we showed that TGF-β inhibition can decrease the metabolic changes associated with cancer cachexia and improve overall survival.

  7. TGF-β Blockade Reduces Mortality and Metabolic Changes in a Validated Murine Model of Pancreatic Cancer Cachexia.

    Science.gov (United States)

    Greco, Stephanie H; Tomkötter, Lena; Vahle, Anne-Kristin; Rokosh, Rae; Avanzi, Antonina; Mahmood, Syed Kashif; Deutsch, Michael; Alothman, Sara; Alqunaibit, Dalia; Ochi, Atsuo; Zambirinis, Constantinos; Mohaimin, Tasnima; Rendon, Mauricio; Levie, Elliot; Pansari, Mridul; Torres-Hernandez, Alejandro; Daley, Donnele; Barilla, Rocky; Pachter, H Leon; Tippens, Daniel; Malik, Hassan; Boutajangout, Allal; Wisniewski, Thomas; Miller, George

    2015-01-01

    Cancer cachexia is a debilitating condition characterized by a combination of anorexia, muscle wasting, weight loss, and malnutrition. This condition affects an overwhelming majority of patients with pancreatic cancer and is a primary cause of cancer-related death. However, few, if any, effective therapies exist for both treatment and prevention of this syndrome. In order to develop novel therapeutic strategies for pancreatic cancer cachexia, appropriate animal models are necessary. In this study, we developed and validated a syngeneic, metastatic, murine model of pancreatic cancer cachexia. Using our model, we investigated the ability of transforming growth factor beta (TGF-β) blockade to mitigate the metabolic changes associated with cachexia. We found that TGF-β inhibition using the anti-TGF-β antibody 1D11.16.8 significantly improved overall mortality, weight loss, fat mass, lean body mass, bone mineral density, and skeletal muscle proteolysis in mice harboring advanced pancreatic cancer. Other immunotherapeutic strategies we employed were not effective. Collectively, we validated a simplified but useful model of pancreatic cancer cachexia to investigate immunologic treatment strategies. In addition, we showed that TGF-β inhibition can decrease the metabolic changes associated with cancer cachexia and improve overall survival.

  8. Portal vein-circulating tumor cells predict liver metastases in patients with resectable pancreatic cancer.

    Science.gov (United States)

    Bissolati, Massimiliano; Sandri, Maria Teresa; Burtulo, Giovanni; Zorzino, Laura; Balzano, Gianpaolo; Braga, Marco

    2015-02-01

    Pancreatic cancer patients underwent surgical resection often present distant metastases early after surgery. Detection of circulating tumor cells (CTCs) has been correlated to a worse oncological outcome in patients with advanced pancreatic cancer. The objective of this pilot study is to investigate the possible prognostic role of CTCs in patients undergoing surgery for pancreatic cancer. In 20 patients undergoing pancreatic resection, 10 mL blood sample was collected intraoperatively from both systemic circulation (SC) and portal vein (PV). Blood sample was analyzed for CTCs with CellSearch® system. All patients underwent an oncologic follow-up for at least 3 years, quarterly. CTCs were detected in nine (45%) patients: five patients had CTCs in PV only, three patients in both SC and PV, and one patient in SC only. CTC-positive and CTC-negative patients were similar for demographics and cancer stage pattern. No significant differences were found in both overall and disease-free survival between CTC-positive and CTC-negative patients. At 3-year follow-up, portal vein CTC-positive patients presented a higher rate of liver metastases than CTC-negative patients (53 vs. 8%, p = 0.038). CTCs were found in 45% of the patients. No correlation between CTCs and survival was found. The presence of CTCs in portal vein has been associated to higher rate of liver metastases after surgery.

  9. Cancer

    Science.gov (United States)

    ... cancer Non-Hodgkin lymphoma Ovarian cancer Pancreatic cancer Testicular cancer Thyroid cancer Uterine cancer Symptoms Symptoms of cancer ... tumor Obesity Pancreatic cancer Prostate cancer Stomach cancer Testicular cancer Throat or larynx cancer Thyroid cancer Patient Instructions ...

  10. Engagement of Patients With Advanced Cancer

    Science.gov (United States)

    2016-11-15

    End of Life; Advanced Cancer; Lung Neoplasm; Gastric Cancer; Colon Cancer; Glioblastoma Multiforme; Head and Neck Neoplasms; Rectum Cancer; Melanoma; Kidney Cancer; Prostate Cancer; Testicular Neoplasms; Liver Cancer; Cancer of Unknown Origin

  11. Challenges of drug resistance in the management of pancreatic cancer.

    LENUS (Irish Health Repository)

    Sheikh, Rizwan

    2012-02-01

    The current treatment of choice for metastatic pancreatic cancer involves single-agent gemcitabine or a combination of gemcitabine with capecitabine or erlotinib (a tyrosine kinase inhibitor). Only 25–30% of patients respond to this treatment and patients who do respond initially ultimately exhibit disease progression. Median survival for pancreatic cancer patients has reached a plateau due to inherent and acquired resistance to these agents. Key molecular factors implicated in this resistance include: deficiencies in drug uptake, alteration of drug targets, activation of DNA repair pathways, resistance to apoptosis and the contribution of the tumor microenvironment. Moreover, for newer agents including tyrosine kinase inhibitors, overexpression of signaling proteins, mutations in kinase domains, activation of alternative pathways, mutations of genes downstream of the target and\\/or amplification of the target represent key challenges for treatment efficacy. Here we will review the contribution of known mechanisms and markers of resistance to key pancreatic cancer drug treatments.

  12. Use of incretin agents and risk of pancreatic cancer

    DEFF Research Database (Denmark)

    Knapen, L M; van Dalem, J; Keulemans, Y C;

    2016-01-01

    of pancreatic cancer in those recently initiating incretin agents is likely to be caused by protopathic bias or other types of unknown distortion. The presence of considerable confounding by disease severity and the lack of a duration-of-use relationship do not support a causal explanation for the association......AIM: To investigate the association between the use of incretin agents and the risk of pancreatic cancer. METHODS: A retrospective population-based cohort study, using data from the Clinical Practice Research Datalink, 2007-2012, was conducted. Patients (n = 182 428) with at least one non......-insulin antidiabetic drug (NIAD) prescription and aged ≥18 years during data collection, were matched one-to-one to control patients without diabetes. Multivariable Cox proportional hazards models and a new user design were used to estimate the hazard ratio (HR) of pancreatic cancer in incretin users (n = 28 370...

  13. The Role of Apoptosis in the Pathology of Pancreatic Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Samm, Nicole; Werner, Kristin; Rückert, Felix; Saeger, Hans Detlev; Grützmann, Robert; Pilarsky, Christian, E-mail: christian.pilarsky@uniklinikum-dresden.de [Department of Visceral-, Thoracic-and Vascular-Surgery, University Hospital Dresden, Dresden (Germany)

    2010-12-23

    Pancreatic cancer is a disease with high resistance to most common therapies and therefore has a poor prognosis, which is partly due to a lack of reaction to apoptotic stimuli. Signal transduction of such stimuli includes a death receptor-mediated extrinsic pathway as well as an intrinsic pathway linked to the mitochondria. Defects in apoptotic pathways and the deregulation of apoptotic proteins, such as Survivin, Bcl-2, Bcl-x{sub L} and Mcl-1, play decisive roles in the development of pancreatic cancer. Investigation of the molecular mechanism allowing tumors to resist apoptotic cell death would lead to an improved understanding of the physiology and the development of new molecular strategies in pancreatic cancer.

  14. The Smad family and its role in pancreatic cancer

    Directory of Open Access Journals (Sweden)

    P Singh

    2011-01-01

    Full Text Available One of the major signaling pathways that determine the tumor aggression and patient outcome in pancreatic cancer is the transforming growth factor-beta (TGF-ß pathway. It is inactivated at various levels in pancreatic cancer and plays a dual role in tumor initiation and progression. The Smad family of proteins transduce signals from the TGF-ß superfamily ligands that regulate cell proliferation, differentiation and death through activation of receptor serine/threonine kinases. This review discusses the structure, function and regulation of various participating Smad family members, and their individual roles in determining the progression and outcome of pancreatic cancer patients, with a special emphasis on Smad4.

  15. Development and controversies of adjuvant therapy for pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    Wan-Yee Lau; Eric C. H. Lai

    2008-01-01

    BACKGROUND:Pancreatic cancer is an aggressive malignancy with a dismal prognosis. Radical surgery provides the only chance for a cure with a 5-year survival rate of 7%-25%. An effective adjuvant therapy is urgently needed to improve the surgical outcome. This review describes the current status of adjuvant therapy for pancreatic cancer, and highlights its controversies. DATA SOURCES:A Medline database search was performed to identify relevant articles using the keywords"pancreatic neoplasm", and"adjuvant therapy". Additional papers were identiifed by a manual search of the references from the key articles. RESULTS:Eight prospective randomized controlled trials (RCTs) on the use of adjuvant chemotherapy and chemoradiation for pancreatic cancer could be identiifed. The results for adjuvant regimens based on systemic 5-lfuorouracil with or without external radiotherapy were conlficting. The recent two RCTs on gemcitabine based regimen gave promising results. CONCLUSIONS:Based on the available data, no standard adjuvant therapy for pancreatic cancer can be established yet. The best adjuvant regimen remains to be determined in large-scale RCTs. Future trials should use a gemcitabine based regimen.

  16. Pancreatic cancer: optimizing treatment options, new, and emerging targeted therapies

    Directory of Open Access Journals (Sweden)

    Chiorean EG

    2015-07-01

    Full Text Available Elena Gabriela Chiorean, Andrew L Coveler Department of Medicine, Division of Oncology, University of Washington, Seattle, WA, USA Abstract: Pancreatic cancer is the fourth leading cause of cancer death in the US and is expected to become the second leading cause of cancer-related deaths in the next decade. Despite 5-fluorouracil/leucovorin with irinotecan and oxaliplatin (FOLFIRINOX and gemcitabine/nab-paclitaxel significantly improving outcomes for metastatic cancer, refractory disease still poses significant challenges. Difficulties with early detection and the inherent chemo- and radio-resistant nature of this malignancy led to attempts to define the sequential biology of pancreatic cancer in order to improve survival outcomes. Pancreatic adenocarcinoma is characterized by several germline or acquired genetic mutations, the most common being KRAS (90%, CDK2NA (90%, TP53 (75%–90%, DPC4/SMAD4 (50%. In addition, the tumor microenvironment, chemoresistant cancer stem cells, and the desmoplastic stroma have been the target of some promising clinical investigations. Among the core pathways reproducibly shown to lead the development and progression of this disease, DNA repair, apoptosis, G1/S cell cycle transition, KRAS, Wnt, Notch, Hedgehog, TGF-beta, and other cell invasion pathways, have been the target of “precision therapeutics”. No single molecularly targeted therapeutic though has been uniformly successful, probably due to the tumor heterogeneity, but biomarker research is evolving and it hopes to select more patients likely to benefit. Recent reports note activity with immunotherapies such as CD40 agonists, CCR2 inhibitors, cancer vaccines, and novel combinations against the immunosuppressive tumor milieu are ongoing. While many obstacles still exist, clearly we are making progress in deciphering the heterogeneity within pancreatic cancers. Integrating conventional and immunological targeting will be the key to effective treatment of

  17. Control of Apoptosis in Treatment and Biology of Pancreatic Cancer.

    Science.gov (United States)

    Modi, Shrey; Kir, Devika; Banerjee, Sulagna; Saluja, Ashok

    2016-02-01

    Pancreatic cancer is estimated to be the 12th most common cancer in the United States in 2014 and yet this malignancy is the fourth leading cause of cancer-related death in the United States. Late detection and resistance to therapy are the major causes for its dismal prognosis. Apoptosis is an actively orchestrated cell death mechanism that serves to maintain tissue homoeostasis. Cancer develops from normal cells by accruing significant changes through one or more mechanisms, leading to DNA damage and mutations, which in a normal cell would induce this programmed cell death pathway. As a result, evasion of apoptosis is one of the hallmarks of cancer cells. PDAC is notoriously resistant to apoptosis, thereby explaining its aggressive nature and resistance to conventional treatment modalities. The current review is focus on understanding different intrinsic and extrinsic pathways in pancreatic cancer that may affect apoptosis in this disease.

  18. Dietary Patterns and Pancreatic Cancer Risk: A Meta-Analysis

    Science.gov (United States)

    Lu, Pei-Ying; Shu, Long; Shen, Shan-Shan; Chen, Xu-Jiao; Zhang, Xiao-Yan

    2017-01-01

    A number of studies have examined the associations between dietary patterns and pancreatic cancer risk, but the findings have been inconclusive. Herein, we conducted this meta-analysis to assess the associations between dietary patterns and the risk of pancreatic cancer. MEDLINE (provided by the National Library of Medicine) and EBSCO (Elton B. Stephens Company) databases were searched for relevant articles published up to May 2016 that identified common dietary patterns. Thirty-two studies met the inclusion criteria and were finally included in this meta-analysis. A reduced risk of pancreatic cancer was shown for the highest compared with the lowest categories of healthy patterns (odds ratio, OR = 0.86; 95% confidence interval, CI: 0.77–0.95; p = 0.004) and light–moderate drinking patterns (OR = 0.90; 95% CI: 0.83–0.98; p = 0.02). There was evidence of an increased risk for pancreatic cancer in the highest compared with the lowest categories of western-type pattern (OR = 1.24; 95% CI: 1.06–1.45; p = 0.008) and heavy drinking pattern (OR = 1.29; 95% CI: 1.10–1.48; p = 0.002). The results of this meta-analysis demonstrate that healthy and light–moderate drinking patterns may decrease the risk of pancreatic cancer, whereas western-type and heavy drinking patterns may increase the risk of pancreatic cancer. Additional prospective studies are needed to confirm these findings. PMID:28067765

  19. Novel pancreatic cancer cell lines derived from genetically engineered mouse models of spontaneous pancreatic adenocarcinoma: applications in diagnosis and therapy.

    Directory of Open Access Journals (Sweden)

    María P Torres

    Full Text Available Pancreatic cancer (PC remains one of the most lethal human malignancies with poor prognosis. Despite all advances in preclinical research, there have not been significant translation of novel therapies into the clinics. The development of genetically engineered mouse (GEM models that produce spontaneous pancreatic adenocarcinoma (PDAC have increased our understanding of the pathogenesis of the disease. Although these PDAC mouse models are ideal for studying potential therapies and specific genetic mutations, there is a need for developing syngeneic cell lines from these models. In this study, we describe the successful establishment and characterization of three cell lines derived from two (PDAC mouse models. The cell line UN-KC-6141 was derived from a pancreatic tumor of a Kras(G12D;Pdx1-Cre (KC mouse at 50 weeks of age, whereas UN-KPC-960 and UN-KPC-961 cell lines were derived from pancreatic tumors of Kras(G12D;Trp53(R172H;Pdx1-Cre (KPC mice at 17 weeks of age. The cancer mutations of these parent mice carried over to the daughter cell lines (i.e. Kras(G12D mutation was observed in all three cell lines while Trp53 mutation was observed only in KPC cell lines. The cell lines showed typical cobblestone epithelial morphology in culture, and unlike the previously established mouse PDAC cell line Panc02, expressed the ductal marker CK19. Furthermore, these cell lines expressed the epithelial-mesenchymal markers E-cadherin and N-cadherin, and also, Muc1 and Muc4 mucins. In addition, these cell lines were resistant to the chemotherapeutic drug Gemcitabine. Their implantation in vivo produced subcutaneous as well as tumors in the pancreas (orthotopic. The genetic mutations in these cell lines mimic the genetic compendium of human PDAC, which make them valuable models with a high potential of translational relevance for examining diagnostic markers and therapeutic drugs.

  20. Possible Role of Autophagy in the Treatment of Pancreatic Cancer with Histone Deacetylase Inhibitors

    Energy Technology Data Exchange (ETDEWEB)

    Rikiishi, Hidemi [Department of Microbiology and Immunology, Tohoku University Graduate School of Dentistry, 4-1 Seiryo-machi, Aoba-ku, Sendai 980-8575 (Japan)

    2010-11-29

    Pancreatic cancer is a lethal disease and notoriously difficult to treat. Only a small proportion is curative by surgical resection, whilst standard chemotherapy for patients with advanced disease has only a modest effect with substantial toxicity. Clearly there is a need for the continual development of novel therapeutic agents to improve the current situation. Currently, there is a bulk of data indicating the important function of autophagy in cancer. While genetic evidence indicates that autophagy functions as a tumor suppressor, it is also apparent that autophagy can promote the survival of established tumors under stress conditions and in response to chemotherapy. This review provides a spectrum of potential pharmacological agents and autophagic approaches to enhance cell killing in pancreatic cancer.

  1. Preoperative assessment and optimization in periampullary and pancreatic cancer

    Directory of Open Access Journals (Sweden)

    S Myatra

    2011-01-01

    Full Text Available Perioperative management of pancreatic and periampullary cancer poses a considerable challenge to the pancreatic surgeon, anesthesiologist, and the intensive care team. The preoperative surgical evaluation of a pancreatic lesion aims to define the nature of the lesion (malignant or benign, stage the tumor, and to determine resectability or other non-surgical treatment options. Patients are often elderly and may have significant comorbidities and malnutrition. Obstructive jaundice may lead to coagulopathy, infection, renal dysfunction, and adverse outcomes. Routine preoperative biliary drainage can result in higher complication rates, and metal stents may be preferred over plastic stents in selected patients with resectable disease. Judicious use of antibiotics and maintaining fluid volume preoperatively can reduce the incidence of infection and renal dysfunction, respectively. Perioperative fluid therapy with hemodynamic optimization using minimally invasive monitoring may help improve outcomes. Careful patient selection, appropriate preoperative evaluation and optimization can greatly contribute to a favorable outcome after major pancreatic resections.

  2. Metastatic pancreatic cancer presenting as linitis plastica of the stomach.

    Science.gov (United States)

    Garg, Shivani; Mulki, Ramzi; Sher, Daniel

    2016-03-08

    Metastatic disease from pancreatic carcinoma involving the stomach is an unusual event, and the pattern of spread in the form of linitis plastica, to our knowledge, has not been reported previously. Local recurrence after curative resection for pancreatic cancer is the most common pattern of disease. We report a case of metastatic pancreatic adenocarcinoma presenting as linitis plastica of the stomach 4 years after curative resection. A 52-year-old man presented with epigastric pain and melaena 4 years after undergoing a Whipple's procedure for a poorly-differentiated pancreatic adenocarcinoma, stage IB; T2N0M0. CT imaging of the abdomen revealed thickening of the gastric wall, and subsequent oesophagogastroduodenoscopy (OGD) revealed diffuse friable erythaematous tissue. The biopsy specimen obtained during the OGD revealed a poorly differentiated adenocarcinoma, with similar appearance to the prior specimen obtained from the pancreas.

  3. Intensity of follow-up after pancreatic cancer resection.

    Science.gov (United States)

    Castellanos, Jason A; Merchant, Nipun B

    2014-03-01

    The prognosis of patients diagnosed with pancreatic adenocarcinoma remains dismal. Of the 15-20 % of patients who are candidates for potentially curative resection, 66-92 % will develop recurrent disease. Although guidelines for surveillance in the postoperative setting exist, they are not evidence based, and there is wide variability of strategies utilized. Current surveillance guidelines as suggested by the National Comprehensive Cancer Network (NCCN) include routine history and physical, measurement of serum cancer-associated antigen 19-9 (CA19-9) levels, and computed tomographic imaging at 3- to 6-month intervals for the first 2 years, and annually thereafter. However, the lack of prospective clinical data examining the efficacy of different surveillance strategies has led to a variability of the intensity of follow-up and a lack of consensus on its necessity and efficacy. Recent therapeutic advances may have the potential to significantly alter survival after recurrence, but a careful consideration of current surveillance strategies should be undertaken to optimize existing approaches in the face of high recurrence and low survival rates.

  4. Nanotechnology for delivery of gemcitabine to treat pancreatic cancer.

    Science.gov (United States)

    Birhanu, Gebremariam; Javar, Hamid Akbari; Seyedjafari, Ehsan; Zandi-Karimi, Ali

    2017-04-01

    Pancreatic cancer (PC) is one of the most deadly and quickly fatal human cancers with a 5-year mortality rate close to 100%. Its prognosis is very poor, mainly because of its hostile biological behavior and late onset of symptoms for clinical diagnosis; these bring limitations on therapeutic interventions. Factors contributing for the difficulties in treating PC include: high rate of drug resistance, fast metastasis to different organs, poor prognosis and relapse of the tumor after therapy. After being approved by US FDA 1997, Gemcitabine (Gem) is the first line and the gold standard drug for all stages of advanced PC till now. However, its efficacy is unsatisfactory, mainly due to; its chemical instability and poor cellular uptake, resulting in an extremely short half-life and low bioavailability. To solve this drawbacks and increase the therapeutic outcome important progress has been achieved in the field of nanotechnology and offers a promising and effective alternative. This review mainly focus on the most commonly investigated nanoparticle (NP) delivery systems of Gem for PC treatment and the latest progresses achieved. Novel nanocarriers with better tumor targeting efficiencies and maximum treatment outcome to treat this deadly due are given much attention.

  5. Prognostic value of metastin expression in human pancreatic cancer

    Directory of Open Access Journals (Sweden)

    Kawaguchi Yoshiya

    2009-01-01

    Full Text Available Abstract Background KiSS-1 was identified as a metastasis-suppressing gene in melanoma cells. The KiSS-1 gene product (metastin was isolated from human placenta as the ligand of GPR54, a G-protein-coupled receptor. The role of metastin and GPR54 in tumor progression is not fully understood. Methods We investigated the clinical significance of metastin and GPR54 expression in pancreatic cancer. We evaluated immunohistochemical expression of metastin and GPR54 in pancreatic ductal adenocarcinoma tissues obtained from 53 consecutive patients who underwent resection between July 2003 and May 2007 at Kyoto University Hospital. In 23 consecutive patients, the plasma metastin level was measured before surgery by enzyme immunoassay. Results Strong immunohistochemical expression of metastin was detected in 13 tumors (24.5%, while strong expression of GPR54 was detected in 30 tumors (56.6%. Tumors that were negative for both metastin and GPR54 expression were significantly larger than tumors that were positive for either metastin or GPR54 (p = 0.047. Recurrence was less frequent in patients who had metastin-positive tumors compared with those who had metastin-negative tumors (38.5% versus 70.0%, p = 0.04. Strong expression of metastin and GPR54 was significantly correlated with longer survival (p = 0.02. Metastin expression by pancreatic cancer was an independent prognostic factor for longer survival (hazard ratio, 2.1; 95% confidence interval, 1.1–4.7; p = 0.03, and the patients with a high plasma metastin level (n = 6 did not die after surgical resection. Conclusion Strong expression of metastin and GPR54 by pancreatic cancer is associated with longer survival. Metastin expression is an independent prognostic factor for the survival of pancreatic cancer patients. The plasma metastin level could become a noninvasive prognostic factor for the assessment of pancreatic cancer.

  6. The role of quantitative mass spectrometry in the discovery of pancreatic cancer biomarkers for translational science.

    Science.gov (United States)

    Ansari, Daniel; Aronsson, Linus; Sasor, Agata; Welinder, Charlotte; Rezeli, Melinda; Marko-Varga, György; Andersson, Roland

    2014-04-05

    In the post-genomic era, it has become evident that genetic changes alone are not sufficient to understand most disease processes including pancreatic cancer. Genome sequencing has revealed a complex set of genetic alterations in pancreatic cancer such as point mutations, chromosomal losses, gene amplifications and telomere shortening that drive cancerous growth through specific signaling pathways. Proteome-based approaches are important complements to genomic data and provide crucial information of the target driver molecules and their post-translational modifications. By applying quantitative mass spectrometry, this is an alternative way to identify biomarkers for early diagnosis and personalized medicine. We review the current quantitative mass spectrometric technologies and analyses that have been developed and applied in the last decade in the context of pancreatic cancer. Examples of candidate biomarkers that have been identified from these pancreas studies include among others, asporin, CD9, CXC chemokine ligand 7, fibronectin 1, galectin-1, gelsolin, intercellular adhesion molecule 1, insulin-like growth factor binding protein 2, metalloproteinase inhibitor 1, stromal cell derived factor 4, and transforming growth factor beta-induced protein. Many of these proteins are involved in various steps in pancreatic tumor progression including cell proliferation, adhesion, migration, invasion, metastasis, immune response and angiogenesis. These new protein candidates may provide essential information for the development of protein diagnostics and targeted therapies. We further argue that new strategies must be advanced and established for the integration of proteomic, transcriptomic and genomic data, in order to enhance biomarker translation. Large scale studies with meta data processing will pave the way for novel and unexpected correlations within pancreatic cancer, that will benefit the patient, with targeted treatment.

  7. Hypoxia Induced Tumor Metabolic Switch Contributes to Pancreatic Cancer Aggressiveness

    Directory of Open Access Journals (Sweden)

    Juan L. Iovanna

    2010-12-01

    Full Text Available Pancreatic ductal adenocarcinoma remains one of the most lethal of all solid tumors with an overall five-year survival rate of only 3–5%. Its aggressive biology and resistance to conventional and targeted therapeutic agents lead to a typical clinical presentation of incurable disease once diagnosed. The disease is characterized by the presence of a dense stroma of fibroblasts and inflammatory cells, termed desmoplasia, which limits the oxygen diffusion in the organ, creating a strong hypoxic environment within the tumor. In this review, we argue that hypoxia is responsible for the highly aggressive and metastatic characteristics of this tumor and drives pancreatic cancer cells to oncogenic and metabolic changes facilitating their proliferation. However, the molecular changes leading to metabolic adaptations of pancreatic cancer cells remain unclear. Cachexia is a hallmark of this disease and illustrates that this cancer is a real metabolic disease. Hence, this tumor must harbor metabolic pathways which are probably tied in a complex inter-organ dialog during the development of this cancer. Such a hypothesis would better explain how under fuel source limitation, pancreatic cancer cells are maintained, show a growth advantage, and develop metastasis.

  8. Hypoxia Induced Tumor Metabolic Switch Contributes to Pancreatic Cancer Aggressiveness

    Energy Technology Data Exchange (ETDEWEB)

    Vasseur, Sophie, E-mail: sophie.vasseur@inserm.fr; Tomasini, Richard; Tournaire, Roselyne; Iovanna, Juan L. [INSERM U624, Stress Cellulaire, Parc Scientifique et Technologique de Luminy, 163 Avenue de Luminy, BP 915,13288 Marseille cedex 9 (France)

    2010-12-16

    Pancreatic ductal adenocarcinoma remains one of the most lethal of all solid tumors with an overall five-year survival rate of only 3–5%. Its aggressive biology and resistance to conventional and targeted therapeutic agents lead to a typical clinical presentation of incurable disease once diagnosed. The disease is characterized by the presence of a dense stroma of fibroblasts and inflammatory cells, termed desmoplasia, which limits the oxygen diffusion in the organ, creating a strong hypoxic environment within the tumor. In this review, we argue that hypoxia is responsible for the highly aggressive and metastatic characteristics of this tumor and drives pancreatic cancer cells to oncogenic and metabolic changes facilitating their proliferation. However, the molecular changes leading to metabolic adaptations of pancreatic cancer cells remain unclear. Cachexia is a hallmark of this disease and illustrates that this cancer is a real metabolic disease. Hence, this tumor must harbor metabolic pathways which are probably tied in a complex inter-organ dialog during the development of this cancer. Such a hypothesis would better explain how under fuel source limitation, pancreatic cancer cells are maintained, show a growth advantage, and develop metastasis.

  9. Comparison of Uncinate Process Cancer and Non-Uncinate Process Pancreatic Head Cancer.

    Science.gov (United States)

    Liu, Chang; Tian, Xiaodong; Xie, Xuehai; Gao, Hongqiao; Zhuang, Yan; Yang, Yinmo

    2016-01-01

    The special anatomical position accounts for unusual clinicopathological features of uncinate process cancer. This study aimed to compare clinicopathological features of patients with uncinate process cancer to patients with non-uncinate process pancreatic head cancer. Total 160 patients with pancreatic head cancer were enrolled and classified into two groups: uncinate process cancer and non-uncinate process pancreatic head cancer. We found that the ratio of vascular invasion was significantly higher in patients with uncinate process cancer than in patients with non-uncinate process pancreatic head cancer. In addition, the rate of R1 resection was significantly higher in patients with uncinate process cancer. Furthermore, the median disease-free survival (11 months vs. 15 months, p=0.043) and overall survival (15 months vs. 19 months, p=0.036) after R0 resection were lower for uncinate process cancer. Locoregional recurrence was more frequent (p=0.017) and earlier (12 months vs. 36 months; p=0.002) in patients with uncinate process cancer than in patients with non-uncinate process pancreatic head cancer. In conclusion, uncinate process cancer is more likely to invade blood vessel and has worse prognosis due to the earlier and more frequent locoregional recurrence.

  10. Pristimerin causes G1 arrest, induces apoptosis, and enhances the chemosensitivity to gemcitabine in pancreatic cancer cells.

    Directory of Open Access Journals (Sweden)

    Yongwei Wang

    Full Text Available Despite rapid advances in chemotherapy and surgical resection strategies, pancreatic cancer remains the fourth leading cause of cancer related deaths in the United States with a 5-year survival rate of less than 5%. Therefore, novel therapeutic agents for the prevention and treatment of pancreatic cancer are urgently needed. The aim of this study was to investigate the effect of pristimerin, a quinonemethide triterpenoid compound isolated from Celastraceae and Hippocrateaceae, on inhibition of cell proliferation and induction of apoptosis in three pancreatic cancer cells, BxPC-3, PANC-1 and AsPC-1, in both monotherapy and in combination with gemcitabine. Treatment with pristimerin decreased the cell proliferation of all three pancreatic cancer cells in a dose- and time-dependent manner. Treatment of pancreatic cancer cells with pristimerin also resulted in G1-phase arrest which was strongly associated with a marked decrease in the level of cyclins (D1 and E and cyclin-dependent kinases (cdk2, cdk4 and cdk6 with concomitant induction of WAF1/p21 and KIP1/p27. Pristimerin treatment also resulted in apoptotic cell death, cleavage of caspase-3, modulation in the expressions of Bcl-2 family proteins, inhibition of the translocation and DNA-binding activity of NF-κB. In addition, pristimerin potentiated the growth inhibition and apoptosis inducing effects of gemcitabine in all three pancreatic cancer cells, at least in part, by inhibiting constitutive as well as gemcitabine-induced activation of NF-κB in both its DNA-binding activity and transcriptional activity. Taken together, these data provide the first evidence that pristimerin has strong potential for development as a novel agent against pancreatic cancer.

  11. Pancreatic Cancer Gene Therapy: From Molecular Targets to Delivery Systems

    Energy Technology Data Exchange (ETDEWEB)

    Fillat, Cristina, E-mail: cristina.fillat@crg.es; Jose, Anabel; Ros, Xavier Bofill-De; Mato-Berciano, Ana; Maliandi, Maria Victoria; Sobrevals, Luciano [Programa Gens i Malaltia, Centre de Regulació Genòmica-CRG, UPF, Parc de Recerca Biomedica de Barcelona-PRBB and Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Barcelona (Spain)

    2011-01-18

    The continuous identification of molecular changes deregulating critical pathways in pancreatic tumor cells provides us with a large number of novel candidates to engineer gene-targeted approaches for pancreatic cancer treatment. Targets—both protein coding and non-coding—are being exploited in gene therapy to influence the deregulated pathways to facilitate cytotoxicity, enhance the immune response or sensitize to current treatments. Delivery vehicles based on viral or non-viral systems as well as cellular vectors with tumor homing characteristics are a critical part of the design of gene therapy strategies. The different behavior of tumoral versus non-tumoral cells inspires vector engineering with the generation of tumor selective products that can prevent potential toxic-associated effects. In the current review, a detailed analysis of the different targets, the delivery vectors, the preclinical approaches and a descriptive update on the conducted clinical trials are presented. Moreover, future possibilities in pancreatic cancer treatment by gene therapy strategies are discussed.

  12. CLINICAL USE OF COMBINED DETECTION WITH TUMOR MARKERS FOR PANCREATIC CANCER

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objective To explore the value of clinical use of combined detection with tumor markers for pancreatic cancer. Methods Tumor markers CA242,CA19-9 and CA50 in serum of 32 patinets with pancreatic cancer;26 patients with non-pancreatic digestive tract cancers and 24 patietns with benign pancreatic or biliary tract diseases were measured by immunoradiometric assay (IRMA). Results The levels of three markers in serum and positive rates of patients with pancreatic cancer were higher than those of other patients. The effect of measurement combining CA242 with CA19-9 was the best. The sensitivity ,specificity and accuracy of diagnosis for pancreatic cancer were 92.6%, 73.8% and 81.2% respectively. The levels of CA242 and CA19-9 were positively relative to burden of pancreatic cancer, and serum levels of these two markers of patients with resectable pancreatic cancer were lower than those with unresectable, but on difference was observed for CA50. Conclusion Combined detection of serum CA242 and CA19-9 could prove the effectual indicator for finding the patients with pancreatic cancer in high risk population or for resectable pancreatic cancer. Pre-operative measurement of serum levels of CA242 and CA19-9 is helpful to evaluate the burden of the tumors and possiblity of resect for pancreatic cancers.

  13. Duodenal Acidity May Increase the Risk of Pancreatic Cancer in the Course of Chronic Pancreatitis: An Etiopathogenetic Hypothesis

    Directory of Open Access Journals (Sweden)

    Talamini G

    2005-03-01

    Full Text Available Chronic pancreatitis patients have an increased risk of developing pancreatic cancer. The cause of this increase has yet to be fully explained but smoking and inflammation may play an important role. To these, we must now add a new potential risk factor, namely duodenal acidity. Patients with chronic pancreatitis very often present pancreatic exocrine insufficiency combined with a persistently low duodenal pH in the postprandial period. The duodenal mucosa in chronic pancreas patients with pancreatic insufficiency has a normal concentration of s-cells and, therefore, the production of secretin is preserved. Pancreatic ductal cells are largely responsible for the amount of bicarbonate and water secretion in response to secretin stimulation. When gastric acid in the duodenum is not well-balanced by alkaline pancreatic secretions, it may induce a prolonged secretin stimulus which interacts with the pancreatic ductal cells resulting in an increased rate of ductular cell activity and turnover. N-Nitroso compounds from tobacco, identified in human pancreatic juice and known to be important carcinogens, may then act on these active cells, thereby increasing the risk of cancer. Duodenal acidity is probably of particular concern in patients who have undergone a duodenum-preserving pancreatic head resection, since, in this anatomic situation, pancreatic juice transits directly via the jejunal loop, bypassing the duodenum. Patients undergoing a Whipple procedure or side-to-side pancreaticojejunostomy are probably less critically affected because secretions transit, at least in part, via the papilla. If the duodenal acidity hypothesis proves correct, then, in addition to stopping smoking, reduction of duodenal acid load in patients with pancreatic insufficiency may help decrease the risk of pancreatic cancer.

  14. Xanthohumol-Mediated Suppression of Notch1 Signaling Is Associated with Antitumor Activity in Human Pancreatic Cancer Cells.

    Science.gov (United States)

    Kunnimalaiyaan, Selvi; Trevino, Jose; Tsai, Susan; Gamblin, T Clark; Kunnimalaiyaan, Muthusamy

    2015-06-01

    Pancreatic cancer remains a lethal disease with limited treatment options. At the time of diagnosis, approximately 80% of these patients present with unresectable tumors caused by either locally advanced lesions or progressive metastatic growth. Therefore, development of novel treatment strategies and new therapeutics is needed. Xanthohumol (XN) has emerged as a potential compound that inhibits various types of cancer, but the molecular mechanism underlying the effects of XN remains unclear. In the present study, we have assessed the efficacy of XN on pancreatic cancer cell lines (AsPC-1, PANC-1, L3.6pl, MiaPaCa-2, 512, and 651) against cell growth in real time and using colony-forming assays. Treatment with XN resulted in reduction in cellular proliferation in a dose- and time-dependent manner. The growth suppression effect of XN in pancreatic cancer cell lines is due to increased apoptosis via the inhibition of the Notch1 signaling pathway, as evidenced by reduction in Notch1, HES-1, and survivin both at mRNA as well as protein levels. Notch1 promoter reporter analysis after XN treatment indicated that XN downregulates Notch promoter activity. Importantly, overexpression of active Notch1 in XN-treated pancreatic cancer cells resulted in negation of growth suppression. Taken together, these findings demonstrate, for the first time, that the growth suppressive effect of XN in pancreatic cancer cells is mainly mediated by Notch1 reduction.

  15. Second Primary Pancreatic Adenocarcinoma Three Years After Successfully Treated Index Esophageal Cancer

    Directory of Open Access Journals (Sweden)

    Nina Nandy

    2014-01-01

    Full Text Available Context Development of a second primary malignancy after an index esophageal cancer is a rare event, primarily due to short survival of patients with esophageal cancer. However, the number of long-term esophageal cancer survivors has been increasing due to advances in early detection and therapy. Case report We report herein a case of pancreatic adenocarcinoma that developed three years after a successfully treated early-stage adenocarcinoma of the esophagus. A 70-year-old Caucasian male presented with vague complaints of nausea, vomiting and abdominal distention, with subsequent development of jaundice. A computed tomography scan of abdomen revealed a 2.9 cm soft tissue mass in the head of the pancreas and the patient underwent a Whipple’s procedure, with pathology confirming the diagnosis of pancreatic adenocarcinoma. Three years previously, the patient was successfully treated for adenocarcinoma of the esophagus via minimally invasive esophagogastrectomy. Despite chemoradiotherapy for localized disease and subsequent systemic chemotherapy for metastatic pancreatic cancer, the patient eventually succumbed to his illness. Conclusion We discuss the association between esophageal cancer and subsequent second malignancies, along with implications for surveillance and therapy.

  16. Metformin Treatment Does Not Inhibit Growth of Pancreatic Cancer Patient-Derived Xenografts.

    Science.gov (United States)

    Lipner, Matthew B; Marayati, Raoud; Deng, Yangmei; Wang, Xianxi; Raftery, Laura; O'Neil, Bert H; Yeh, Jen Jen

    2016-01-01

    There is currently tremendous interest in developing anti-cancer therapeutics targeting cell signaling pathways important for both cancer cell metabolism and growth. Several epidemiological studies have shown that diabetic patients taking metformin have a decreased incidence of pancreatic cancer. This has prompted efforts to evaluate metformin, a drug with negligible toxicity, as a therapeutic modality in pancreatic cancer. Preclinical studies in cell line xenografts and one study in patient-derived xenograft (PDX) models were promising, while recently published clinical trials showed no benefit to adding metformin to combination therapy regimens for locally advanced and metastatic pancreatic cancer. PDX models in which patient tumors are directly engrafted into immunocompromised mice have been shown to be excellent preclinical models for biomarker discovery and therapeutic development. We evaluated the response of four PDX tumor lines to metformin treatment and found that all four of our PDX lines were resistant to metformin. We found that the mechanisms of resistance may occur through lack of sustained activation of adenosine monophosphate-activated protein kinase (AMPK) or downstream reactivation of the mammalian target of rapamycin (mTOR). Moreover, combined treatment with metformin and mTOR inhibitors failed to improve responses in cell lines, which further indicates that metformin alone or in combination with mTOR inhibitors will be ineffective in patients, and that resistance to metformin may occur through multiple pathways. Further studies are required to better understand these mechanisms of resistance and inform potential combination therapies with metformin and existing or novel therapeutics.

  17. Is screening for pancreatic cancer in high-risk groups cost-effective?

    DEFF Research Database (Denmark)

    Jørgensen, Maiken Thyregod; Gerdes, Anne-Marie; Sørensen, Jan;

    2016-01-01

    OBJECTIVE: Pancreatic cancer (PC) is the fourth leading cause of cancer death worldwide, symptoms are few and diffuse, and when the diagnosis has been made only 10-15% would benefit from resection. Surgery is the only potentially curable treatment for pancreatic cancer, and the prognosis seems...... with Hereditary pancreatitis or with a disposition of HP and 40 first-degree relatives of patients with Familial Pancreatic Cancer (FPC) were screened for development of Pancreatic Ductal Adenocarcinoma (PDAC) with yearly endoscopic ultrasound. The cost-effectiveness of screening in comparison with no...

  18. Dynamic Contrast-Enhanced CT in Patients with Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Rie Ø. Eriksen

    2016-09-01

    Full Text Available The aim of this systematic review is to provide an overview of the use of Dynamic Contrast-enhanced Computed Tomography (DCE-CT in patients with pancreatic cancer. This study was composed according to the PRISMA guidelines 2009. The literature search was conducted in PubMed, Cochrane Library, EMBASE, and Web of Science databases to identify all relevant publications. The QUADAS-2 tool was implemented to assess the risk of bias and applicability concerns of each included study. The initial literature search yielded 483 publications. Thirteen articles were included. Articles were categorized into three groups: nine articles concerning primary diagnosis or staging, one article about tumor response to treatment, and three articles regarding scan techniques. In exocrine pancreatic tumors, measurements of blood flow in eight studies and blood volume in seven studies were significantly lower in tumor tissue, compared with measurements in pancreatic tissue outside of tumor, or normal pancreatic tissue in control groups of healthy volunteers. The studies were heterogeneous in the number of patients enrolled and scan protocols. Perfusion parameters measured and analyzed by DCE-CT might be useful in the investigation of characteristic vascular patterns of exocrine pancreatic tumors. Further clinical studies are desired for investigating the potential of DCE-CT in pancreatic tumors.

  19. Genomic analyses identify molecular subtypes of pancreatic cancer.

    Science.gov (United States)

    Bailey, Peter; Chang, David K; Nones, Katia; Johns, Amber L; Patch, Ann-Marie; Gingras, Marie-Claude; Miller, David K; Christ, Angelika N; Bruxner, Tim J C; Quinn, Michael C; Nourse, Craig; Murtaugh, L Charles; Harliwong, Ivon; Idrisoglu, Senel; Manning, Suzanne; Nourbakhsh, Ehsan; Wani, Shivangi; Fink, Lynn; Holmes, Oliver; Chin, Venessa; Anderson, Matthew J; Kazakoff, Stephen; Leonard, Conrad; Newell, Felicity; Waddell, Nick; Wood, Scott; Xu, Qinying; Wilson, Peter J; Cloonan, Nicole; Kassahn, Karin S; Taylor, Darrin; Quek, Kelly; Robertson, Alan; Pantano, Lorena; Mincarelli, Laura; Sanchez, Luis N; Evers, Lisa; Wu, Jianmin; Pinese, Mark; Cowley, Mark J; Jones, Marc D; Colvin, Emily K; Nagrial, Adnan M; Humphrey, Emily S; Chantrill, Lorraine A; Mawson, Amanda; Humphris, Jeremy; Chou, Angela; Pajic, Marina; Scarlett, Christopher J; Pinho, Andreia V; Giry-Laterriere, Marc; Rooman, Ilse; Samra, Jaswinder S; Kench, James G; Lovell, Jessica A; Merrett, Neil D; Toon, Christopher W; Epari, Krishna; Nguyen, Nam Q; Barbour, Andrew; Zeps, Nikolajs; Moran-Jones, Kim; Jamieson, Nigel B; Graham, Janet S; Duthie, Fraser; Oien, Karin; Hair, Jane; Grützmann, Robert; Maitra, Anirban; Iacobuzio-Donahue, Christine A; Wolfgang, Christopher L; Morgan, Richard A; Lawlor, Rita T; Corbo, Vincenzo; Bassi, Claudio; Rusev, Borislav; Capelli, Paola; Salvia, Roberto; Tortora, Giampaolo; Mukhopadhyay, Debabrata; Petersen, Gloria M; Munzy, Donna M; Fisher, William E; Karim, Saadia A; Eshleman, James R; Hruban, Ralph H; Pilarsky, Christian; Morton, Jennifer P; Sansom, Owen J; Scarpa, Aldo; Musgrove, Elizabeth A; Bailey, Ulla-Maja Hagbo; Hofmann, Oliver; Sutherland, Robert L; Wheeler, David A; Gill, Anthony J; Gibbs, Richard A; Pearson, John V; Waddell, Nicola; Biankin, Andrew V; Grimmond, Sean M

    2016-03-01

    Integrated genomic analysis of 456 pancreatic ductal adenocarcinomas identified 32 recurrently mutated genes that aggregate into 10 pathways: KRAS, TGF-β, WNT, NOTCH, ROBO/SLIT signalling, G1/S transition, SWI-SNF, chromatin modification, DNA repair and RNA processing. Expression analysis defined 4 subtypes: (1) squamous; (2) pancreatic progenitor; (3) immunogenic; and (4) aberrantly differentiated endocrine exocrine (ADEX) that correlate with histopathological characteristics. Squamous tumours are enriched for TP53 and KDM6A mutations, upregulation of the TP63∆N transcriptional network, hypermethylation of pancreatic endodermal cell-fate determining genes and have a poor prognosis. Pancreatic progenitor tumours preferentially express genes involved in early pancreatic development (FOXA2/3, PDX1 and MNX1). ADEX tumours displayed upregulation of genes that regulate networks involved in KRAS activation, exocrine (NR5A2 and RBPJL), and endocrine differentiation (NEUROD1 and NKX2-2). Immunogenic tumours contained upregulated immune networks including pathways involved in acquired immune suppression. These data infer differences in the molecular evolution of pancreatic cancer subtypes and identify opportunities for therapeutic development.

  20. The genetics of nicotine dependence: Relationship to pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    Stewart L MacLeod; Parimal Chowdhury

    2006-01-01

    Smoking of tobacco products continues to be a major cause of worldwide health problems. Epidemiological studies have shown that tobacco smoking is the greatest risk factor for the development of pancreatic cancer.Smokers who are able to quit smoking can reduce their risk of pancreatic cancer by nearly 50% within two years, however, their risk of developing pancreatic cancer remains higher than that of non-smokers for 10 years. Nicotine is the major psychoactive substance in tobacco, and is responsible for tobacco dependence and addiction. Recent evidence suggests that individuals have genetically based differences in their ability to metabolize nicotine, as well as genetic differences in the psychological reward pathways that may influence individual response to smoking initiation, dependence,addiction and cessation. Numerous associations have been reported between smoking behavior and genetic polymorphisms in genes that are responsible for nicotine metabolism. Tn addition, polymorphisms in genes that encode neurotransmitters and transporters that function in psychological reward pathways have been implicated in differences in smoking behavior. However,there is a large degree of between-study variability that demonstrates the need for larger, well-controlled casecontrol studies to identify target genes and deduce mechanisms that account for the genetic basis of interindividual differences in smoking behavior. Understanding the genetic factors that increase susceptibility to tobacco addiction may result in more effective tobacco cessation programs which will, in turn, reduce the incidence of tobacco related disease, including pancreatic cancer.

  1. Knowledge discovery for pancreatic cancer using inductive logic programming.

    Science.gov (United States)

    Qiu, Yushan; Shimada, Kazuaki; Hiraoka, Nobuyoshi; Maeshiro, Kensei; Ching, Wai-Ki; Aoki-Kinoshita, Kiyoko F; Furuta, Koh

    2014-08-01

    Pancreatic cancer is a devastating disease and predicting the status of the patients becomes an important and urgent issue. The authors explore the applicability of inductive logic programming (ILP) method in the disease and show that the accumulated clinical laboratory data can be used to predict disease characteristics, and this will contribute to the selection of therapeutic modalities of pancreatic cancer. The availability of a large amount of clinical laboratory data provides clues to aid in the knowledge discovery of diseases. In predicting the differentiation of tumour and the status of lymph node metastasis in pancreatic cancer, using the ILP model, three rules are developed that are consistent with descriptions in the literature. The rules that are identified are useful to detect the differentiation of tumour and the status of lymph node metastasis in pancreatic cancer and therefore contributed significantly to the decision of therapeutic strategies. In addition, the proposed method is compared with the other typical classification techniques and the results further confirm the superiority and merit of the proposed method.

  2. Pyruvate Kinase M2 and Lactate Dehydrogenase A Are Overexpressed in Pancreatic Cancer and Correlate with Poor Outcome.

    Science.gov (United States)

    Mohammad, Goran Hamid; Olde Damink, S W M; Malago, Massimo; Dhar, Dipok Kumar; Pereira, Stephen P

    2016-01-01

    Pancreatic cancer has a 5-year survival rate of less than 4%. Despite advances in diagnostic technology, pancreatic cancer continues to be diagnosed at a late and incurable stage. Accurate biomarkers for early diagnosis and to predict treatment response are urgently needed. Since alteration of glucose metabolism is one of the hallmarks of cancer cells, we proposed that pyruvate kinase type M2 (M2PK) and lactate dehydrogenase A (LDHA) enzymes could represent novel diagnostic markers and potential therapeutic targets in pancreatic cancer. In 266 tissue sections from normal pancreas, pancreatic cystic neoplasms, pancreatic intraepithelial neoplasia (PanIN) and cancer, we evaluated the expression of PKM2, LDHA, Ki-67 and CD8+ by immunohistochemistry and correlated these markers with clinicopathological characteristics and patient survival. PKM2 and LDHA expression was also assessed by Western blot in 10 human pancreatic cancer cell lines. PKM2 expression increased progressively from cyst through PanIN to cancer, whereas LDHA was overexpressed throughout the carcinogenic process. All but one cell line showed high expression of both proteins. Patients with strong PKM2 and LDHA expression had significantly worse survival than those with weak PKM2 and/or LDHA expression (7.0 months vs. 27.9 months, respectively, p = 0.003, log rank test). The expression of both PKM2 and LDHA correlated directly with Ki-67 expression, and inversely with intratumoral CD8+ cell count. PKM2 was significantly overexpressed in poorly differentiated tumours and both PKM2 and LDHA were overexpressed in larger tumours. Multivariable analysis showed that combined expression of PKM2 and LDHA was an independent poor prognostic marker for survival. In conclusion, our results demonstrate a high expression pattern of two major glycolytic enzymes during pancreatic carcinogenesis, with increased expression in aggressive tumours and a significant adverse effect on survival.

  3. Pyruvate Kinase M2 and Lactate Dehydrogenase A Are Overexpressed in Pancreatic Cancer and Correlate with Poor Outcome.

    Directory of Open Access Journals (Sweden)

    Goran Hamid Mohammad

    Full Text Available Pancreatic cancer has a 5-year survival rate of less than 4%. Despite advances in diagnostic technology, pancreatic cancer continues to be diagnosed at a late and incurable stage. Accurate biomarkers for early diagnosis and to predict treatment response are urgently needed. Since alteration of glucose metabolism is one of the hallmarks of cancer cells, we proposed that pyruvate kinase type M2 (M2PK and lactate dehydrogenase A (LDHA enzymes could represent novel diagnostic markers and potential therapeutic targets in pancreatic cancer. In 266 tissue sections from normal pancreas, pancreatic cystic neoplasms, pancreatic intraepithelial neoplasia (PanIN and cancer, we evaluated the expression of PKM2, LDHA, Ki-67 and CD8+ by immunohistochemistry and correlated these markers with clinicopathological characteristics and patient survival. PKM2 and LDHA expression was also assessed by Western blot in 10 human pancreatic cancer cell lines. PKM2 expression increased progressively from cyst through PanIN to cancer, whereas LDHA was overexpressed throughout the carcinogenic process. All but one cell line showed high expression of both proteins. Patients with strong PKM2 and LDHA expression had significantly worse survival than those with weak PKM2 and/or LDHA expression (7.0 months vs. 27.9 months, respectively, p = 0.003, log rank test. The expression of both PKM2 and LDHA correlated directly with Ki-67 expression, and inversely with intratumoral CD8+ cell count. PKM2 was significantly overexpressed in poorly differentiated tumours and both PKM2 and LDHA were overexpressed in larger tumours. Multivariable analysis showed that combined expression of PKM2 and LDHA was an independent poor prognostic marker for survival. In conclusion, our results demonstrate a high expression pattern of two major glycolytic enzymes during pancreatic carcinogenesis, with increased expression in aggressive tumours and a significant adverse effect on survival.

  4. Glycemic load, glycemic index, and pancreatic cancer risk in the Netherlands Cohort Study

    NARCIS (Netherlands)

    Heinen, M.M.; Verhage, B.A.J.; Lumey, L.H.; Brants, H.A.M.; Goldbohm, R.A.; Brandt, P.A. van den

    2008-01-01

    Background: Recent studies of pancreatic cancer suggest a role for hyperinsulinemia in carcinogenesis. Because insulin is secreted in response to elevated blood glucose concentrations, dietary factors that increase these concentrations may be important in pancreatic carcinogenesis. Objective: The ob

  5. Pancreatic cancer genomes reveal aberrations in axon guidance pathway genes.

    Science.gov (United States)

    Biankin, Andrew V; Waddell, Nicola; Kassahn, Karin S; Gingras, Marie-Claude; Muthuswamy, Lakshmi B; Johns, Amber L; Miller, David K; Wilson, Peter J; Patch, Ann-Marie; Wu, Jianmin; Chang, David K; Cowley, Mark J; Gardiner, Brooke B; Song, Sarah; Harliwong, Ivon; Idrisoglu, Senel; Nourse, Craig; Nourbakhsh, Ehsan; Manning, Suzanne; Wani, Shivangi; Gongora, Milena; Pajic, Marina; Scarlett, Christopher J; Gill, Anthony J; Pinho, Andreia V; Rooman, Ilse; Anderson, Matthew; Holmes, Oliver; Leonard, Conrad; Taylor, Darrin; Wood, Scott; Xu, Qinying; Nones, Katia; Fink, J Lynn; Christ, Angelika; Bruxner, Tim; Cloonan, Nicole; Kolle, Gabriel; Newell, Felicity; Pinese, Mark; Mead, R Scott; Humphris, Jeremy L; Kaplan, Warren; Jones, Marc D; Colvin, Emily K; Nagrial, Adnan M; Humphrey, Emily S; Chou, Angela; Chin, Venessa T; Chantrill, Lorraine A; Mawson, Amanda; Samra, Jaswinder S; Kench, James G; Lovell, Jessica A; Daly, Roger J; Merrett, Neil D; Toon, Christopher; Epari, Krishna; Nguyen, Nam Q; Barbour, Andrew; Zeps, Nikolajs; Kakkar, Nipun; Zhao, Fengmei; Wu, Yuan Qing; Wang, Min; Muzny, Donna M; Fisher, William E; Brunicardi, F Charles; Hodges, Sally E; Reid, Jeffrey G; Drummond, Jennifer; Chang, Kyle; Han, Yi; Lewis, Lora R; Dinh, Huyen; Buhay, Christian J; Beck, Timothy; Timms, Lee; Sam, Michelle; Begley, Kimberly; Brown, Andrew; Pai, Deepa; Panchal, Ami; Buchner, Nicholas; De Borja, Richard; Denroche, Robert E; Yung, Christina K; Serra, Stefano; Onetto, Nicole; Mukhopadhyay, Debabrata; Tsao, Ming-Sound; Shaw, Patricia A; Petersen, Gloria M; Gallinger, Steven; Hruban, Ralph H; Maitra, Anirban; Iacobuzio-Donahue, Christine A; Schulick, Richard D; Wolfgang, Christopher L; Morgan, Richard A; Lawlor, Rita T; Capelli, Paola; Corbo, Vincenzo; Scardoni, Maria; Tortora, Giampaolo; Tempero, Margaret A; Mann, Karen M; Jenkins, Nancy A; Perez-Mancera, Pedro A; Adams, David J; Largaespada, David A; Wessels, Lodewyk F A; Rust, Alistair G; Stein, Lincoln D; Tuveson, David A; Copeland, Neal G; Musgrove, Elizabeth A; Scarpa, Aldo; Eshleman, James R; Hudson, Thomas J; Sutherland, Robert L; Wheeler, David A; Pearson, John V; McPherson, John D; Gibbs, Richard A; Grimmond, Sean M

    2012-11-15

    Pancreatic cancer is a highly lethal malignancy with few effective therapies. We performed exome sequencing and copy number analysis to define genomic aberrations in a prospectively accrued clinical cohort (n = 142) of early (stage I and II) sporadic pancreatic ductal adenocarcinoma. Detailed analysis of 99 informative tumours identified substantial heterogeneity with 2,016 non-silent mutations and 1,628 copy-number variations. We define 16 significantly mutated genes, reaffirming known mutations (KRAS, TP53, CDKN2A, SMAD4, MLL3, TGFBR2, ARID1A and SF3B1), and uncover novel mutated genes including additional genes involved in chromatin modification (EPC1 and ARID2), DNA damage repair (ATM) and other mechanisms (ZIM2, MAP2K4, NALCN, SLC16A4 and MAGEA6). Integrative analysis with in vitro functional data and animal models provided supportive evidence for potential roles for these genetic aberrations in carcinogenesis. Pathway-based analysis of recurrently mutated genes recapitulated clustering in core signalling pathways in pancreatic ductal adenocarcinoma, and identified new mutated genes in each pathway. We also identified frequent and diverse somatic aberrations in genes described traditionally as embryonic regulators of axon guidance, particularly SLIT/ROBO signalling, which was also evident in murine Sleeping Beauty transposon-mediated somatic mutagenesis models of pancreatic cancer, providing further supportive evidence for the potential involvement of axon guidance genes in pancreatic carcinogenesis.

  6. Targeted Alpha Therapy Approach to the Management of Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Ross C. Smith

    2011-04-01

    Full Text Available Evidence for the efficacy of targeted alpha therapy for the control of pancreatic cancer in preclinical models is reviewed. Results are given for in vitro pancreatic cancer cells and clusters and micro-metastatic cancer lesions in vivo. Two complementary targeting vectors are examined. These are the C595 monoclonal antibody that targets the MUC1 antigen and the PAI2 ligand that targets the uPA receptor. The expression of the tumor-associated antigen MUC-1 and the uPA receptor on three pancreatic cancer cell lines is reported for cell clusters, human mouse xenografts and lymph node metastases, as well as for human pancreatic cancer tissues, using immuno-histochemistry, confocal microscopy and flow cytometry. The targeting vectors C595 and PAI2 were labeled with the alpha emitting radioisotope 213Bi using the chelators cDTPA and CHX-A″ to form the alpha-conjugates (AC. Cell clusters were incubated with the AC and examined at 48 hours. Apoptosis was documented using the TUNEL assay. In vivo, the anti-proliferative effect for tumors was tested at two days post-subcutaneous cell inoculation. Mice were injected with different concentrations of AC by local or systemic administration. Changes in tumor progression were assessed by tumor size. MUC-1 and uPA are strongly expressed on CFPAC-1, PANC-1 and moderate expression was found CAPAN-1 cell clusters and tumor xenografts. The ACs can target pancreatic cells and regress cell clusters (~100 µm diameter, causing apoptosis in some 70–90 % of cells. At two days post-cell inoculation in mice, a single local injection of 74 MBq/kg of AC causes complete inhibition of tumor growth. Systemic injections of 111, 222 and 333 MBq/kg of alpha-conjugate caused significant tumor growth delay in a dose dependent manner after 16 weeks, compared with the non-specific control at 333 MBq/kg. Cytotoxicity was assessed by the MTS and TUNEL assays. The C595 and PAI2-alpha conjugates are indicated for the treatment of

  7. Endoscopic ultrasonography guided celiac plexus neurolysis and celiac plexus block in the management of pain due to pancreatic cancer and chronic pancreatitis

    Institute of Scientific and Technical Information of China (English)

    Anthony J Michaels; Peter V Draganov

    2007-01-01

    Pain is a common symptom of pancreatic disease and is frequently difficult to manage. Pain relief provided by narcotics is often suboptimal and is associated with significant side effects. An alternative approach to pain management in pancreatic disease is the use of celiac plexus block (CPB) or neurolysis (CPN). Originally performed by anesthesiologists and radiologists via a posterior approach, recent advances in endoscopic ultrasonography (EUS) have made this technique an attractive alternative. EUS guided celiac plexus block/neurolysis is simple to perform and avoids serious complications such as paraplegia or pneumothorax that are associated with the posterior approach. EUS guided CPN should be considered first line therapy in patients with pain due to pancreatic cancer. It provides superior pain control compared to traditional management with narcotics. A trend for improved survival in pancreatic cancer patients treated with CPN has been reported,but larger studies are needed to confirm this finding.At this time, the use of EUS guided CPB cannot be recommended as routine therapy for pain in chronic pancreatitis since only one-half of the patients experience pain reduction and the beneficial effect tends to be short lived. EUS guided CPB and CPN should be used as part of a multidisciplinary team approach for pain management.

  8. Pancreatitis-diabetes-pancreatic cancer: summary of an NIDDK-NCI workshop.

    Science.gov (United States)

    Andersen, Dana K; Andren-Sandberg, Åke; Duell, Eric J; Goggins, Michael; Korc, Murray; Petersen, Gloria M; Smith, Jill P; Whitcomb, David C

    2013-11-01

    A workshop sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and the National Cancer Institute (NCI) on "Pancreatitis-Diabetes-Pancreatic Cancer" focused on the risk factors of chronic pancreatitis (CP) and diabetes mellitus (DM) on the development of pancreatic ductal adenocarcinoma (PDAC). Sessions were held on (a) an overview of the problem of PDAC; (b) CP as a risk factor of PDAC; (c) DM as a risk factor of PDAC; (d) pancreatogenic, or type 3c, DM; (e) genomic associations of CP, DM, and PDAC; (f) surveillance of high-risk populations and early detection of PDAC; and (g) effects of DM treatment on PDAC. Recent data and current understandings of the mechanisms of CP- and DM-associated factors on PDAC development were discussed, and a detailed review of the possible risks of DM treatment on the development of PDAC was provided by representatives from academia, industry, and the Food and Drug Administration. The current status of possible biomarkers of PDAC and surveillance strategies for high-risk populations were discussed, and the gaps in knowledge and opportunities for further research were elucidated. A broad spectrum of expertise of the speakers and the discussants provided an unusually productive workshop, the highlights of which are summarized in the accompanying article.

  9. Gene profile identifies zinc transporters differentially expressed in normal human organs and human pancreatic cancer.

    Science.gov (United States)

    Yang, J; Zhang, Y; Cui, X; Yao, W; Yu, X; Cen, P; Hodges, S E; Fisher, W E; Brunicardi, F C; Chen, C; Yao, Q; Li, M

    2013-03-01

    Deregulated expression of zinc transporters was linked to several cancers. However, the detailed expression profile of all human zinc transporters in normal human organs and in human cancer, especially in pancreatic cancer is not available. The objectives of this study are to investigate the complete expression patterns of 14 ZIP and 10 ZnT transporters in a large number of normal human organs and in human pancreatic cancer tissues and cell lines. We examined the expression patterns of ZIP and ZnT transporters in 22 different human organs and tissues, 11 pairs of clinical human pancreatic cancer specimens and surrounding normal/benign tissues, as well as 10 established human pancreatic cancer cell lines plus normal human pancreatic ductal epithelium (HPDE) cells, using real time RT-PCR and immunohistochemistry. The results indicate that human zinc transporters have tissue specific expression patterns, and may play different roles in different organs or tissues. Almost all the ZIPs except for ZIP4, and most ZnTs were down-regulated in human pancreatic cancer tissues compared to the surrounding benign tissues. The expression patterns of individual ZIPs and ZnTs are similar among different pancreatic cancer lines. Those results and our previous studies suggest that ZIP4 is the only zinc transporter that is significantly up-regulated in human pancreatic cancer and might be the major zinc transporter that plays an important role in pancreatic cancer growth. ZIP4 might serve as a novel molecular target for pancreatic cancer diagnosis and therapy.

  10. Pancreatic cancer: optimizing treatment options, new, and emerging targeted therapies.

    Science.gov (United States)

    Chiorean, Elena Gabriela; Coveler, Andrew L

    2015-01-01

    Pancreatic cancer is the fourth leading cause of cancer death in the US and is expected to become the second leading cause of cancer-related deaths in the next decade. Despite 5-fluorouracil/leucovorin with irinotecan and oxaliplatin (FOLFIRINOX) and gemcitabine/nab-paclitaxel significantly improving outcomes for metastatic cancer, refractory disease still poses significant challenges. Difficulties with early detection and the inherent chemo- and radio-resistant nature of this malignancy led to attempts to define the sequential biology of pancreatic cancer in order to improve survival outcomes. Pancreatic adenocarcinoma is characterized by several germline or acquired genetic mutations, the most common being KRAS (90%), CDK2NA (90%), TP53 (75%-90%), DPC4/SMAD4 (50%). In addition, the tumor microenvironment, chemoresistant cancer stem cells, and the desmoplastic stroma have been the target of some promising clinical investigations. Among the core pathways reproducibly shown to lead the development and progression of this disease, DNA repair, apoptosis, G1/S cell cycle transition, KRAS, Wnt, Notch, Hedgehog, TGF-beta, and other cell invasion pathways, have been the target of "precision therapeutics". No single molecularly targeted therapeutic though has been uniformly successful, probably due to the tumor heterogeneity, but biomarker research is evolving and it hopes to select more patients likely to benefit. Recent reports note activity with immunotherapies such as CD40 agonists, CCR2 inhibitors, cancer vaccines, and novel combinations against the immunosuppressive tumor milieu are ongoing. While many obstacles still exist, clearly we are making progress in deciphering the heterogeneity within pancreatic cancers. Integrating conventional and immunological targeting will be the key to effective treatment of this deadly disease.

  11. Impact of Noncoding Satellite Repeats on Pancreatic Cancer Metastasis

    Science.gov (United States)

    2015-11-01

    microenvironment. noncoding RNA | genome evolution | cancer immunology The recent development of total RNA sequencing has alloweda better appreciation of the...Award Number: W81XWH-13-1-0237 TITLE: IImpact of Noncoding Satellite Repeats on Pancreatic Cancer Metastasis PRINCIPAL INVESTIGATOR: David T...0704-0188 Public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing

  12. Dietary mutagen exposure and risk of pancreatic cancer.

    Science.gov (United States)

    Li, Donghui; Day, Rena Sue; Bondy, Melissa L; Sinha, Rashmi; Nguyen, Nga T; Evans, Douglas B; Abbruzzese, James L; Hassan, Manal M

    2007-04-01

    To investigate the association between dietary exposure to food mutagens and risk of pancreatic cancer, we conducted a hospital-based case-control study at the University of Texas M. D. Anderson Cancer Center during June 2002 to May 2006. A total of 626 cases and 530 noncancer controls were frequency matched for race, sex and age (+/-5 years). Dietary exposure information was collected via personal interview using a meat preparation questionnaire. A significantly greater portion of the cases than controls showed a preference to well-done pork, bacon, grilled chicken, and pan-fried chicken, but not to hamburger and steak. Cases had a higher daily intake of food mutagens and mutagenicity activity (revertants per gram of daily meat intake) than controls did. The daily intakes of 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx) and benzo(a)pyrene (BaP), as well as the mutagenic activity, were significant predictors for pancreatic cancer (P = 0.008, 0.031, and 0.029, respectively) with adjustment of other confounders. A significant trend of elevated cancer risk with increasing DiMeIQx intake was observed in quintile analysis (P(trend) = 0.024). A higher intake of dietary mutagens (those in the two top quintiles) was associated with a 2-fold increased risk of pancreatic cancer among those without a family history of cancer but not among those with a family history of cancer. A possible synergistic effect of dietary mutagen exposure and smoking was observed among individuals with the highest level of exposure (top 10%) to PhIP and BaP, P(interaction) = 0.09 and 0.099, respectively. These data support the hypothesis that dietary mutagen exposure alone and in interaction with other factors contribute to the development of pancreatic cancer.

  13. Novel curcumin-loaded magnetic nanoparticles for pancreatic cancer treatment.

    Science.gov (United States)

    Yallapu, Murali M; Ebeling, Mara C; Khan, Sheema; Sundram, Vasudha; Chauhan, Neeraj; Gupta, Brij K; Puumala, Susan E; Jaggi, Meena; Chauhan, Subhash C

    2013-08-01

    Curcumin (CUR), a naturally occurring polyphenol derived from the root of Curcuma longa, has showed potent anticancer and cancer prevention activity in a variety of cancers. However, the clinical translation of CUR has been significantly hampered due to its extensive degradation, suboptimal pharmacokinetics, and poor bioavailability. To address these clinically relevant issues, we have developed a novel CUR-loaded magnetic nanoparticle (MNP-CUR) formulation. Herein, we have evaluated the in vitro and in vivo therapeutic efficacy of this novel MNP-CUR formulation in pancreatic cancer. Human pancreatic cancer cells (HPAF-II and Panc-1) exhibited efficient internalization of the MNP-CUR formulation in a dose-dependent manner. As a result, the MNP-CUR formulation effectively inhibited growth of HPAF-II and Panc-1 cells in cell proliferation and colony formation assays. The MNP-CUR formulation suppressed pancreatic tumor growth in an HPAF-II xenograft mouse model and improved the survival of mice by delaying tumor growth. The growth-inhibitory effect of MNP-CUR formulation correlated with the suppression of proliferating cell nuclear antigen (PCNA), B-cell lymphoma-extra large (Bcl-xL), induced myeloid leukemia cell differentiation protein (Mcl-1), cell surface-associated Mucin 1 (MUC1), collagen I, and enhanced membrane β-catenin expression. MNP-CUR formulation did not show any sign of hemotoxicity and was stable after incubation with human serum proteins. In addition, the MNP-CUR formulation improved serum bioavailability of CUR in mice up to 2.5-fold as compared with free CUR. Biodistribution studies show that a significant amount of MNP-CUR formulation was able to reach the pancreatic xenograft tumor(s), which suggests its clinical translational potential. In conclusion, this study suggests that our novel MNP-CUR formulation can be valuable for the treatment of pancreatic cancer.

  14. Pathobiological implications of MUC16 expression in pancreatic cancer.

    Directory of Open Access Journals (Sweden)

    Dhanya Haridas

    Full Text Available MUC16 (CA125 belongs to a family of high-molecular weight O-glycosylated proteins known as mucins. While MUC16 is well known as a biomarker in ovarian cancer, its expression pattern in pancreatic cancer (PC, the fourth leading cause of cancer related deaths in the United States, remains unknown. The aim of our study was to analyze the expression of MUC16 during the initiation, progression and metastasis of PC for possible implication in PC diagnosis, prognosis and therapy. In this study, a microarray containing tissues from healthy and PC patients was used to investigate the differential protein expression of MUC16 in PC. MUC16 mRNA levels were also measured by RT-PCR in the normal human pancreatic, pancreatitis, and PC tissues. To investigate its expression pattern during PC metastasis, tissue samples from the primary pancreatic tumor and metastases (from the same patient in the lymph nodes, liver, lung and omentum from Stage IV PC patients were analyzed. To determine its association in the initiation of PC, tissues from PC patients containing pre-neoplastic lesions of varying grades were stained for MUC16. Finally, MUC16 expression was analyzed in 18 human PC cell lines. MUC16 is not expressed in the normal pancreatic ducts and is strongly upregulated in PC and detected in pancreatitis tissue. It is first detected in the high-grade pre-neoplastic lesions preceding invasive adenocarcinoma, suggesting that its upregulation is a late event during the initiation of this disease. MUC16 expression appears to be stronger in metastatic lesions when compared to the primary tumor, suggesting a role in PC metastasis. We have also identified PC cell lines that express MUC16, which can be used in future studies to elucidate its functional role in PC. Altogether, our results reveal that MUC16 expression is significantly increased in PC and could play a potential role in the progression of this disease.

  15. Pancreatic cancer: Translational research aspects and clinical implications

    Institute of Scientific and Technical Information of China (English)

    Daniel Ansari; Bi-Cheng Chen; Lei Dong; Meng-Tao Zhou; Roland Andersson

    2012-01-01

    Despite improvements in surgical techniques and adjuvant chemotherapy,the overall mortality rates in pancreatic cancer have generally remained relatively unchanged and the 5-year survival rate is actually below 2%.This paper will address the importance of achieving an early diagnosis and identifying markers for prognosis and response to therapy such as genes,proteins,microRNAs or epigenetic modifications.However,there are still major hurdles when translating investigational biomarkers into routine clinical practice.Furthermore,novel ways of secondary screening in high-risk individuals,such as artificial neural networks and modern imaging,will be discussed.Drug resistance is ubiquitous in pancreatic cancer.Several mechanisms of drug resistance have already been revealed,including human equilibrative nucleoside transporter-1 status,multidrug resistance proteins,aberrant signaling pathways,microRNAs,stromal influence,epithelial-mesenchymal transition-type cells and recently the presence of cancer stem cells/cancer-initiating cells.These factors must be considered when developing more customized types of intervention ("personalized medicine").In the future,multifunctional nanoparticles that combine a specific targeting agent,an imaging probe,a cell-penetrating agent,a biocompatible polymer and an anti-cancer drug may become valuable for the management of patients with pancreatic cancer.

  16. Metformin and pancreatic cancer: Is there a role?

    Science.gov (United States)

    De Souza, Andre; Khawaja, Khadija Irfan; Masud, Faisal; Saif, Muhammad Wasif

    2016-02-01

    Pancreatic cancer is the fourth leading cause of cancer-related deaths in the USA, with a 5-year survival rate of 6 %. Anti-hyperglycemic treatments for type 2 diabetes mellitus that induce hyperinsulinemia (i.e., sulfonylureas) are thought to increase cancer risk, whereas treatments that lower insulin resistance and hyperinsulinemia (i.e., metformin) are considered cancer prevention strategies. Metformin is a cornerstone in the treatment of diabetes mellitus type 2. Retrospective studies have shown a survival benefit in diabetic patients with many solid tumors including pancreatic cancer that have been treated with metformin compared with patients treated with insulin or sulfonylureas. Metformin influences various cellular pathways, including activation of the LKB1/AMPK pathway, inhibition of cell division, promotion of apoptosis and autophagy, down-regulation of circulating insulin, and activation of the immune system. Ongoing research is redefining our understanding about how metformin modulates the molecular pathways implicated in pancreatic cancer. The authors review the topic critically and also give their opinion. Further studies investigating the effect of metformin in combination with chemotherapy, targeted agents, or radiation therapy are undergoing. In addition, the role of metabolic and other biomarkers is needed.

  17. The Hemostasis Apparatus in Pancreatic Cancer and Its Importance beyond Thrombosis

    Directory of Open Access Journals (Sweden)

    Hussein Echrish

    2011-01-01

    Full Text Available Laboratory evidence of aberrant coagulation is found in the majority of patients with advanced pancreatic cancer and a clinical consequence of this is the high incidence and prevalence of vascular thromboembolic events. Other sequelae are hypothesized to be the facilitation and acceleration of mechanisms that define the malignant phenotype, such as invasion, trafficking and anchoring, establishing the metastatic niche and inducing angiogenesis. We review the in vitro and preclinical evidence that supports the role of the coagulation apparatus in the metastatic process of pancreatic cancer, with a particular emphasis on interaction of this pathway with clinically-targeted growth factor receptor pathways. Links between hemostasis, angiogenesis and epidermal growth factor pathways and their significance as therapeutic targets are considered.

  18. The Hemostasis Apparatus in Pancreatic Cancer and Its Importance beyond Thrombosis

    Energy Technology Data Exchange (ETDEWEB)

    Echrish, Hussein; Madden, Leigh A.; Greenman, John [Centre for Biomedical Research, PGMI, University of Hull, Hull, HU6 7RX (United Kingdom); Maraveyas, Anthony, E-mail: anthony.maraveyas@hey.nhs.uk [Queen' s Centre for Oncology and Haematology, Castle Hill Hospital, Castle Road, Cottingham, HU16 5JQ (United Kingdom)

    2011-01-11

    Laboratory evidence of aberrant coagulation is found in the majority of patients with advanced pancreatic cancer and a clinical consequence of this is the high incidence and prevalence of vascular thromboembolic events. Other sequelae are hypothesized to be the facilitation and acceleration of mechanisms that define the malignant phenotype, such as invasion, trafficking and anchoring, establishing the metastatic niche and inducing angiogenesis. We review the in vitro and preclinical evidence that supports the role of the coagulation apparatus in the metastatic process of pancreatic cancer, with a particular emphasis on interaction of this pathway with clinically-targeted growth factor receptor pathways. Links between hemostasis, angiogenesis and epidermal growth factor pathways and their significance as therapeutic targets are considered.

  19. GSK3β and β-Catenin Modulate Radiation Cytotoxicity in Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Richard L. Watson

    2010-05-01

    Full Text Available BACKGROUND: Knowledge of factors and mechanisms contributing to the inherent radioresistance of pancreatic cancer may improve cancer treatment. Irradiation inhibits glycogen synthase kinase 3β (GSK3β by phosphorylation at serine 9. In turn, release of cytosolic membrane β-catenin with subsequent nuclear translocation promotes survival. Both GSK3β and β-catenin have been implicated in cancer cell proliferation and resistance to death. METHODS: We investigated pancreatic cancer cell survival after radiation in vitro and in vivo, with a particular focus on the role of the function of the GSK3β/β-catenin axis. RESULTS: Lithium chloride, RNAi-medicated silencing of GSK3β, or the expression of a kinase dead mutant GSK3β resulted in radioresistance of Panc1 and BxPC3 pancreatic cancer cells. Conversely, ectopic expression of a constitutively active form of GSK3β resulted in radiosensitization of Panc1 cells. GSK3β silencing increased radiation-induced β-catenin target gene expression asmeasured by studies of AXIN2 and LEF1 transcript levels. Western blot analysis of total and phosphorylated levels of GSK3β and β-catenin showed that GSK3β inhibition resulted in stabilization of β-catenin. Xenografts of both BxPC3 and Panc1 with targeted silencing of GSK3β exhibited radioresistance in vivo. Silencing of β-catenin resulted in radiosensitization, whereas a nondegradable β-catenin construct induced radioresistance. CONCLUSIONS: These data support the hypothesis that GSK3β modulates the cellular response to radiation in a β-catenin-dependent mechanism. Further understanding of this pathway may enhance the development of clinical trials combining drugs inhibiting β-catenin activation with radiation and chemotherapy in locally advanced pancreatic cancer.

  20. Tuft Cell Regulation of miRNAs in Pancreatic Cancer

    Science.gov (United States)

    2014-12-01

    scientific research publication ( PLoS One . 2015 Feb 27;10(2):e0118933), and one scientific presentation at the 2014 American Pancreatic Association...adenocarcinoma, PI: Courtney W. Houchen, April, 2015 – Mar, 2020). • Successfully published recently in journal PLoS ONE (Qu et al., PLoS One . 2015 Feb 27;10(2...pancreatic cancer. PloS one . 2013;8(9):e73940. doi: 10.1371/journal.pone.0073940. PubMed PMID: 24040120; PubMed Central PMCID: PMC3767662. 3

  1. Adjuvant Strategies for Resectable Pancreatic Cancer: Have We Made Progress?

    Directory of Open Access Journals (Sweden)

    Suzanne Russo

    2012-03-01

    Full Text Available Substantial controversy remains regarding the optimal adjuvant treatment for patients with resectable pancreatic adenocarcinoma. Despite improvements in radiation techniques, systemic therapies, and incorporation of targeted agents, the 5-year survival rates for early stage patients remains less than 25% and the optimal adjuvant treatment approach remains unclear. Here we summarize the data presented at the 2012 American Society of Clinical Oncology (ASCO Gastrointestinal Cancers Symposium regarding controversial issues surrounding the role, timing, and selection of patients for adjuvant chemoradiation strategies following curative resection for pancreatic adenocarcinoma. (Abstracts #301, #333, and #206.

  2. Prognostic value of metastin expression in human pancreatic cancer

    OpenAIRE

    Nagai, Kazuyuki; Doi, Ryuichiro; Katagiri, Fumihiko; Ito, Tatsuo; Kida, Atsushi; Koizumi, Masayuki; Masui, Toshihiko; Kawaguchi, Yoshiya; Tomita, Kenji; Oishi, Shinya; Fujii, Nobutaka; Uemoto, Shinji

    2009-01-01

    Background KiSS-1 was identified as a metastasis-suppressing gene in melanoma cells. The KiSS-1 gene product (metastin) was isolated from human placenta as the ligand of GPR54, a G-protein-coupled receptor. The role of metastin and GPR54 in tumor progression is not fully understood. Methods We investigated the clinical significance of metastin and GPR54 expression in pancreatic cancer. We evaluated immunohistochemical expression of metastin and GPR54 in pancreatic ductal adenocarcinoma tissue...

  3. Prognostic value of metastin expression in human pancreatic cancer.

    OpenAIRE

    Nagai, Kazuyuki; Doi, Ryuichiro; Katagiri, Fumihiko; Ito, Tatsuo; Kida, Atsushi; Koizumi, Masayuki; Masui, Toshihiko; Kawaguchi, Yoshiya; Tomita, Kenji; Oishi, Shinya; Fujii, Nobutaka; Uemoto, Shinji

    2009-01-01

    [Background]KiSS-1 was identified as a metastasis-suppressing gene in melanoma cells. The KiSS-1 gene product (metastin) was isolated from human placenta as the ligand of GPR54, a G-protein-coupled receptor. The role of metastin and GPR54 in tumor progression is not fully understood. [Methods]We investigated the clinical significance of metastin and GPR54 expression in pancreatic cancer. We evaluated immunohistochemical expression of metastin and GPR54 in pancreatic ductal adenocarcinoma tiss...

  4. Prognostic value of metastin expression in human pancreatic cancer

    OpenAIRE

    Kawaguchi Yoshiya; Masui Toshihiko; Koizumi Masayuki; Kida Atsushi; Ito Tatsuo; Katagiri Fumihiko; Doi Ryuichiro; Nagai Kazuyuki; Tomita Kenji; Oishi Shinya; Fujii Nobutaka; Uemoto Shinji

    2009-01-01

    Abstract Background KiSS-1 was identified as a metastasis-suppressing gene in melanoma cells. The KiSS-1 gene product (metastin) was isolated from human placenta as the ligand of GPR54, a G-protein-coupled receptor. The role of metastin and GPR54 in tumor progression is not fully understood. Methods We investigated the clinical significance of metastin and GPR54 expression in pancreatic cancer. We evaluated immunohistochemical expression of metastin and GPR54 in pancreatic ductal adenocarcino...

  5. Targeting notch to eradicate pancreatic cancer stem cells for cancer therapy.

    Science.gov (United States)

    Wang, Zhiwei; Ahmad, Aamir; Li, Yiwei; Azmi, Asfar S; Miele, Lucio; Sarkar, Fazlul H

    2011-04-01

    Pancreatic cancer is the most aggressive malignant disease once it is diagnosed and it remains the fourth leading cause of cancer-related death in the U.S.A. Recent data indicates that the Notch signaling pathway plays an important role in the development and progression of pancreatic cancer. Emerging evidence also suggests that the activation of the Notch signaling pathway is mechanistically associated with molecular characteristics of cancer stem cells (CSCs) in pancreatic cancer. Moreover, CSCs are known to be highly drug-resistant, suggesting that targeted inactivation of Notch signaling would be useful for overcoming drug resistance and the elimination of CSCs. This review describes the roles of the Notch signaling pathway in pancreatic cancer with a special emphasis on its novel functions in the regulation of pancreatic CSC. Moreover, the review also proposes that targeting the Notch signaling pathway by natural agents may represent a novel strategy for overcoming drug resistance and the elimination of CSCs, which would be useful for the successful treatment of patients diagnosed with pancreatic cancer.

  6. Pancreatic cancer-Palliative therapy:stenting%胰腺癌:姑息性支架术治疗

    Institute of Scientific and Technical Information of China (English)

    U. Wahnschaffe; M. Kraft; S. Turi; M. M. Lerch

    2007-01-01

    Pancreatic cancer remains a common and very lethal malignancy with a median survival of approximately 6 months. Surgical resection offers the only potentially curative approach but many patients (80% or more) are ineligible for this kind of therapy, because of age, comorbidities, or locally advanced or metastatic disease that does not benefit from resection.Thus, for many patients with pancreatic cancer treatment remains palliative and endoscopic therapy to relieve bile duct or gastric outlet obstruction becomes of special importance. Although both surgical and non surgical palliative procedures can relieve biiiary and duodenal obstruction particularly endoscopic treatment with plastic prostheses or self expanding metal stents was shown to be not only highly effective but also to be burdened with only few complications. The present article summarizes the palliative endoscopic treatment in patients with non resectable pancreatic cancer.

  7. Phenethyl isothiocyanate inhibits proliferation and induces apoptosis in pancreatic cancer cells in vitro and in a MIAPaca2 xenograft animal model.

    Science.gov (United States)

    Stan, Silvia D; Singh, Shivendra V; Whitcomb, David C; Brand, Randall E

    2014-01-01

    Pancreatic cancer is often diagnosed at an advanced stage and it has a poor prognosis that points to an increased need to develop effective chemoprevention strategies for this disease. We examined the ability of phenethyl isothiocyanate (PEITC), a naturally occurring isothiocyanate found in cruciferous vegetables, to inhibit the growth of pancreatic cancer cells in vitro and in a MIAPaca2 xenograft animal model. Exposure to PEITC inhibited pancreatic cancer cell growth in a dose-dependent manner, with an IC50 of approximately 7 μmol/L. PEITC treatment induced G2/M phase cell cycle arrest, downregulated the antiapoptotic proteins Bcl-2 and Bcl-XL, upregulated the proapoptotic protein Bak, and suppressed Notch 1 and 2 levels. In addition, treatment with PEITC induced cleavage of poly-(ADP-ribose) polymerase and led to increased cytoplasmic histone-associated DNA fragmentation and subdiploid (apoptotic) fraction in pancreatic cancer cells. Oral administration of PEITC suppressed the growth of pancreatic cancer cells in a MIAPaca2 xenograft animal model. Our data show that PEITC exerts its inhibitory effect on pancreatic cancer cells through several mechanisms, including G2/M phase cell cycle arrest and induction of apoptosis, and supports further investigation of PEITC as a chemopreventive agent for pancreatic cancer.

  8. Adamantyl Retinoid-Related Molecules Induce Apoptosis in Pancreatic Cancer Cells by Inhibiting IGF-1R and Wnt/β-Catenin Pathways

    Directory of Open Access Journals (Sweden)

    Lulu Farhana

    2012-01-01

    Full Text Available Pancreatic carcinoma has a dismal prognosis as it often presents as locally advanced or metastatic. We have found that exposure to adamantyl-substituted retinoid-related (ARR compounds 3-Cl-AHPC and AHP3 resulted in growth inhibition and apoptosis induction in PANC-1, Capan-2, and MiaPaCa-2 pancreatic cancer cell lines. In addition, AHP3 and 3-Cl-AHPC inhibited growth and induced apoptosis in spheres derived from the CD44+/CD24+ (CD133+/EpCAM+ stem-like cell population isolated from the pancreatic cancer cell lines. 3-Cl-AHPC-induced apoptosis was preceded by decreasing expression of IGF-1R, cyclin D1, β-catenin, and activated Notch-1 in the pancreatic cancer cell lines. Decreased IGF-1R expression inhibited PANC-1 proliferation, enhanced 3-Cl-AHPC-mediated apoptosis, and significantly decreased sphere formation. 3-Cl-AHPC inhibited the Wnt/β-catenin pathway as indicated by decreased β-catenin nuclear localization and inhibited Wnt/β-catenin activation of transcription factor TCF/LEF. Knockdown of β-catenin using sh-RNA also induced apoptosis and inhibited growth in pancreatic cancer cells. Thus, 3-Cl-AHPC and AHP3 induce apoptosis in pancreatic cancer cells and cancer stem-like cells and may serve as an important potential therapeutic agent in the treatment of pancreatic cancer.

  9. Oligonucleotide microarray identifies genes differentially expressed during tumorigenesis of DMBA-induced pancreatic cancer in rats.

    Directory of Open Access Journals (Sweden)

    Jun-Chao Guo

    Full Text Available The extremely dismal prognosis of pancreatic cancer (PC is attributed, at least in part, to lack of early diagnosis. Therefore, identifying differentially expressed genes in multiple steps of tumorigenesis of PC is of great interest. In the present study, a 7,12-dimethylbenzanthraene (DMBA-induced PC model was established in male Sprague-Dawley rats. The gene expression profile was screened using an oligonucleotide microarray, followed by real-time quantitative polymerase chain reaction (qRT-PCR and immunohistochemical staining validation. A total of 661 differentially expressed genes were identified in stages of pancreatic carcinogenesis. According to GO classification, these genes were involved in multiple molecular pathways. Using two-way hierarchical clustering analysis, normal pancreas, acute and chronic pancreatitis, PanIN, early and advanced pancreatic cancer were completely discriminated. Furthermore, 11 upregulated and 142 downregulated genes (probes were found by Mann-Kendall trend Monotone test, indicating homologous genes of rat and human. The qRT-PCR and immunohistochemistry analysis of CXCR7 and UBe2c, two of the identified genes, confirmed the microarray results. In human PC cell lines, knockdown of CXCR7 resulted in decreased migration and invasion. Collectively, our data identified several promising markers and therapeutic targets of PC based on a comprehensive screening and systemic validation.

  10. Oligonucleotide microarray identifies genes differentially expressed during tumorigenesis of DMBA-induced pancreatic cancer in rats.

    Science.gov (United States)

    Guo, Jun-Chao; Li, Jian; Yang, Ying-Chi; Zhou, Li; Zhang, Tai-Ping; Zhao, Yu-Pei

    2013-01-01

    The extremely dismal prognosis of pancreatic cancer (PC) is attributed, at least in part, to lack of early diagnosis. Therefore, identifying differentially expressed genes in multiple steps of tumorigenesis of PC is of great interest. In the present study, a 7,12-dimethylbenzanthraene (DMBA)-induced PC model was established in male Sprague-Dawley rats. The gene expression profile was screened using an oligonucleotide microarray, followed by real-time quantitative polymerase chain reaction (qRT-PCR) and immunohistochemical staining validation. A total of 661 differentially expressed genes were identified in stages of pancreatic carcinogenesis. According to GO classification, these genes were involved in multiple molecular pathways. Using two-way hierarchical clustering analysis, normal pancreas, acute and chronic pancreatitis, PanIN, early and advanced pancreatic cancer were completely discriminated. Furthermore, 11 upregulated and 142 downregulated genes (probes) were found by Mann-Kendall trend Monotone test, indicating homologous genes of rat and human. The qRT-PCR and immunohistochemistry analysis of CXCR7 and UBe2c, two of the identified genes, confirmed the microarray results. In human PC cell lines, knockdown of CXCR7 resulted in decreased migration and invasion. Collectively, our data identified several promising markers and therapeutic targets of PC based on a comprehensive screening and systemic validation.

  11. Feasibility of alternating induction and maintenance chemotherapy in pancreatic cancer.

    Science.gov (United States)

    Hann, Alexander; Bohle, Wolfram; Egger, Jan; Zoller, Wolfram

    2017-01-31

    Chemotherapy regimens for pancreatic ductal adenocarcinoma (PDAC) have changed since the introduction of FOLFIRINOX. Due to toxicity, dosage and number of applied cycles are limited. In analogy to chemotherapy strategies in colon cancer we used a scheme of induction, maintenance and re-induction therapy in PDAC to alleviate such toxicities and increase the number of applied cycles. Here we report first experiences with this approach. Data of all patients who received FOLFIRINOX for metastatic or locally advanced PDAC in our center using induction chemotherapy followed by maintenance therapy from 2011 until November 2016 was collected and analyzed retrospectively. Progression free survival was assessed starting induction therapy until progressive disease (PD) during maintenance or treatment pause (PFS1) and until progression during re-induction therapy (PFS2). 13 patients received induction therapy which was followed by maintenance therapy. Re-induction due to PD during therapy was applied in 11 patients. The median PFS1 was 10.6 months (95% CI; 6.7-14.4), PFS2 was 14.1 months (95% CI; 8.2-19.9) and overall survival was 18.3 months (95% CI; 14.8-21.8). The use of FOLFIRINOX as induction, followed by maintenance and re-induction therapy in case of PD is feasible in the treatment of PDAC and might lead to a prolonged PFS with less toxicity.

  12. Targeted diagnostic magnetic nanoparticles for medical imaging of pancreatic cancer.

    Science.gov (United States)

    Rosenberger, I; Strauss, A; Dobiasch, S; Weis, C; Szanyi, S; Gil-Iceta, L; Alonso, E; González Esparza, M; Gómez-Vallejo, V; Szczupak, B; Plaza-García, S; Mirzaei, S; Israel, L L; Bianchessi, S; Scanziani, E; Lellouche, J-P; Knoll, P; Werner, J; Felix, K; Grenacher, L; Reese, T; Kreuter, J; Jiménez-González, M

    2015-09-28

    Highly aggressive cancer types such as pancreatic cancer possess a mortality rate of up to 80% within the first 6months after diagnosis. To reduce this high mortality rate, more sensitive diagnostic tools allowing an early stage medical imaging of even very small tumours are needed. For this purpose, magnetic, biodegradable nanoparticles prepared using recombinant human serum albumin (rHSA) and incorporated iron oxide (maghemite, γ-Fe2O3) nanoparticles were developed. Galectin-1 has been chosen as target receptor as this protein is upregulated in pancreatic cancer and its precursor lesions but not in healthy pancreatic tissue nor in pancreatitis. Tissue plasminogen activator derived peptides (t-PA-ligands), that have a high affinity to galectin-1 have been chosen as target moieties and were covalently attached onto the nanoparticle surface. Improved targeting and imaging properties were shown in mice using single photon emission computed tomography-computer tomography (SPECT-CT), a handheld gamma camera, and magnetic resonance imaging (MRI).

  13. Prognosis Relevance of Serum Cytokines in Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Carolina Torres

    2015-01-01

    Full Text Available The overall survival of patients with pancreatic ductal adenocarcinoma is extremely low. Although gemcitabine is the standard used chemotherapy for this disease, clinical outcomes do not reflect significant improvements, not even when combined with adjuvant treatments. There is an urgent need for prognosis markers to be found. The aim of this study was to analyze the potential value of serum cytokines to find a profile that can predict the clinical outcome in patients with pancreatic cancer and to establish a practical prognosis index that significantly predicts patients’ outcomes. We have conducted an extensive analysis of serum prognosis biomarkers using an antibody array comprising 507 human cytokines. Overall survival was estimated using the Kaplan-Meier method. Univariate and multivariate Cox’s proportional hazard models were used to analyze prognosis factors. To determine the extent that survival could be predicted based on this index, we used the leave-one-out cross-validation model. The multivariate model showed a better performance and it could represent a novel panel of serum cytokines that correlates to poor prognosis in pancreatic cancer. B7-1/CD80, EG-VEGF/PK1, IL-29, NRG1-beta1/HRG1-beta1, and PD-ECGF expressions portend a poor prognosis for patients with pancreatic cancer and these cytokines could represent novel therapeutic targets for this disease.

  14. Circulating myeloid-derived suppressor cells in patients with pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    Xiao-Dong Xu; Jun Hu; Min Wang; Feng Peng; Rui Tian; Xing-Jun Guo; Yu Xie; Ren-Yi Qin

    2016-01-01

    BACKGROUND: Myeloid-derived suppressor cells (MDSCs) are heterogeneous cell types that suppress T-cell responses in cancer patients and animal models, some MDSC subpopula-tions are increased in patients with pancreatic cancer. The present study was to investigate a specific subset of MDSCs in patients with pancreatic cancer and the mechanism of MDSCs increase in these patients. METHODS: Myeloid cells from whole blood were collected from 37 patients with pancreatic cancer, 17 with cholangiocarcinoma, and 47 healthy controls. Four pancreatic cancer cell lines were co-culturedwithnormalperipheralbloodmononuclearcells(PBMCs) to test the effect of tumor cells on the conversion of PBMCs to MDSCs. Levels of granulocyte-macrophage colony-stimulating factor (GM-CSF) and arginase activity in the plasma of cancer patients were analyzed by enzyme-linked immunosorbent assay. RESULTS: CD14+/CD11b+/HLA-DR- MDSCs were increased in patients with pancreatic or bile duct cancer compared with those in healthy controls, and this increase was correlated with clinical cancer stage. Pancreatic cancer cell lines induced PBMCs to MDSCs in a dose-dependent manner. GM-CSF and arginase activity levels were significantly increased in the se-rum of patients with pancreatic cancer. CONCLUSIONS: MDSCsweretumorrelated:tumorcellsinduced PBMCs to MDSCs in a dose-dependent manner and circulating CD14+/CD11b+/HLA-DR- MDSCs in pancreatic cancer patients were positively correlated with tumor burden. MDSCs might be useful markers for pancreatic cancer detection and progression.

  15. Duodenal Toxicity After Fractionated Chemoradiation for Unresectable Pancreatic Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kelly, Patrick; Das, Prajnan; Pinnix, Chelsea C.; Beddar, Sam; Briere, Tina; Pham, Mary; Krishnan, Sunil; Delclos, Marc E. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Crane, Christopher H., E-mail: ccrane@mdanderson.org [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

    2013-03-01

    Purpose: Improving local control is critical to improving survival and quality of life for patients with locally advanced unresectable pancreatic cancer (LAPC). However, previous attempts at radiation dose escalation have been limited by duodenal toxicity. In order to guide future studies, we analyzed the clinical and dosimetric factors associated with duodenal toxicity in patients undergoing fractionated chemoradiation for LAPC. Methods and Materials: Medical records and treatment plans of 106 patients with LAPC who were treated with chemoradiation between July 2005 and June 2010 at our institution were reviewed. All patients received neoadjuvant and concurrent chemotherapy. Seventy-eight patients were treated with conventional radiation to 50.4 Gy in 28 fractions; 28 patients received dose-escalated radiation therapy (range, 57.5-75.4 Gy in 28-39 fractions). Treatment-related toxicity was graded according to Common Terminology Criteria for Adverse Events, version 4.0. Univariate and multivariate analyses were performed to assess prognostic influence of clinical, pathologic, and treatment-related factors by using Kaplan-Meier and Cox regression methods. Results: Twenty patients had treatment-related duodenal toxicity events, such as duodenal inflammation, ulceration, and bleeding. Four patients had grade 1 events, 8 had grade 2, 6 had grade 3, 1 had grade 4, and 1 had grade 5. On univariate analysis, a toxicity grade ≥2 was associated with tumor location, low platelet count, an absolute volume (cm{sup 3}) receiving a dose of at least 55 Gy (V{sub 55} {sub Gy} > 1 cm{sup 3}), and a maximum point dose >60 Gy. Of these factors, only V{sub 55} {sub Gy} ≥1 cm{sup 3} was associated with duodenal toxicity on multivariate analysis (hazard ratio, 6.7; range, 2.0-18.8; P=.002). Conclusions: This study demonstrates that a duodenal V{sub 55} {sub Gy} >1 cm{sup 3} is an important dosimetric predictor of grade 2 or greater duodenal toxicity and establishes it as a

  16. Developmental Pathways Direct Pancreatic Cancer Initiation from Its Cellular Origin

    Directory of Open Access Journals (Sweden)

    Maximilian Reichert

    2016-01-01

    Full Text Available Pancreatic ductal adenocarcinoma (PDA is characterized by an extremely poor prognosis, since it is usually diagnosed at advanced stages. In order to employ tools for early detection, a better understanding of the early stages of PDA development from its main precursors, pancreatic intraepithelial neoplasia (PanIN, and intraductal papillary mucinous neoplasm (IPMN is needed. Recent studies on murine PDA models have identified a different exocrine origin for PanINs and IPMNs. In both processes, developmental pathways direct the initiation of PDA precursors from their cellular ancestors. In this review, the current understanding of early PDA development is summarized.

  17. Molecular mechanism of bitter melon juice efficacy against pancreatic cancer. | Division of Cancer Prevention

    Science.gov (United States)

    DESCRIPTION (provided by applicant): Pancreatic cancer (PanC) is an aggressive disease;median life of PanC patients post-diagnosis is been tested in several clinical trials for its anti-diabetic effects and has plenty of human safety data. We, therefore, anticipate that the positive outcomes from the proposed studies will provide compelling rationale for initiating clinical trials to establish BMJ activity against human pancreatic cancer. |

  18. Omeprazole inhibits proliferation and modulates autophagy in pancreatic cancer cells.

    Directory of Open Access Journals (Sweden)

    Andrej Udelnow

    Full Text Available BACKGROUND: Omeprazole has recently been described as a modulator of tumour chemoresistance, although its underlying molecular mechanisms remain controversial. Since pancreatic tumours are highly chemoresistant, a logical step would be to investigate the pharmacodynamic, morphological and biochemical effects of omeprazole on pancreatic cancer cell lines. METHODOLOGY/PRINCIPAL FINDINGS: Dose-effect curves of omeprazole, pantoprazole, gemcitabine, 5-fluorouracil and the combinations of omeprazole and 5-fluorouracil or gemcitabine were generated for the pancreatic cancer cell lines MiaPaCa-2, ASPC-1, Colo357, PancTu-1, Panc1 and Panc89. They revealed that omeprazole inhibited proliferation at probably non-toxic concentrations and reversed the hormesis phenomena of 5-fluorouracil. Electron microscopy showed that omeprazole led to accumulation of phagophores and early autophagosomes in ASPC-1 and MiaPaCa-2 cells. Signal changes indicating inhibited proliferation and programmed cell death were found by proton NMR spectroscopy of both cell lines when treated with omeprazole which was identified intracellularly. Omeprazole modulates the lysosomal transport pathway as shown by Western blot analysis of the expression of LAMP-1, Cathepsin-D and β-COP in lysosome- and Golgi complex containing cell fractions. Acridine orange staining revealed that the pump function of the vATPase was not specifically inhibited by omeprazole. Gene expression of the autophagy-related LC3 gene as well as of Bad, Mdr-1, Atg12 and the vATPase was analysed after treatment of cells with 5-fluorouracil and omeprazole and confirmed the above mentioned results. CONCLUSIONS: We hypothesise that omeprazole interacts with the regulatory functions of the vATPase without inhibiting its pump function. A modulation of the lysosomal transport pathway and autophagy is caused in pancreatic cancer cells leading to programmed cell death. This may circumvent common resistance mechanisms of

  19. Nutritional status and nutritional support before and after pancreatectomy for pancreatic cancer and chronic pancreatitis.

    Science.gov (United States)

    Karagianni, Vasiliki Th; Papalois, Apostolos E; Triantafillidis, John K

    2012-12-01

    Cachexia, malnutrition, significant weight loss, and reduction in food intake due to anorexia represent the most important pathophysiological consequences of pancreatic cancer. Pathophysiological consequences result also from pancreatectomy, the type and severity of which differ significantly and depend on the type of the operation performed. Nutritional intervention, either parenteral or enteral, needs to be seen as a method of support in pancreatic cancer patients aiming at the maintenance of the nutritional and functional status and the prevention or attenuation of cachexia. Oral nutrition could reduce complications while restoring quality of life. Enteral nutrition in the post-operative period could also reduce infective complications. The evidence for immune-enhanced feed in patients undergoing pancreaticoduodenectomy for pancreatic cancer is supported by the available clinical data. Nutritional support during the post-operative period on a cyclical basis is preferred because it is associated with low incidence of gastric stasis. Postoperative total parenteral nutrition is indicated only to those patients who are unable to be fed orally or enterally. Thus nutritional deficiency is a relatively widesoread and constant finding suggesting that we must optimise the nutritional status both before and after surgery.

  20. Effect of Protein Hydrolysates on Pancreatic Cancer Cells

    DEFF Research Database (Denmark)

    Ossum, Carlo G.; Andersen, Lisa Lystbæk; Nielsen, Henrik Hauch

    Effect of Fish Protein Hydrolysates on Pancreatic Cancer Cells Carlo G. Ossum1, Lisa Lystbæk Andersen2, Henrik Hauch Nielsen2, Else K. Hoffmann1, and Flemming Jessen2 1University of Copenhagen, Department of Biology, Denmark, 2Technical University of Denmark (DTU), National Food Institute, Denmark...... hydrolysates obtained by enzymatic hydrolysis on cancer cell proliferation. Skin and belly flap muscle from trout were hydrolysed with the unspecific proteases Alcalase, Neutrase, or UE1 (all from Novozymes, Bagsværd, Denmark) to a hydrolysis degree of 1-15%. The hydrolysates were tested for biological...... activities affecting cell proliferation and ability to modulate caspase activity in pancreatic cancer cells COLO357 and BxPC-3 in vitro. A number of the hydrolysates showed caspase promoting activity; in particular products containing muscle tissue, i.e. belly flap, were able to stimulate caspase activity...

  1. Imaging pancreatic cancer using bioconjugated InP quantum dots.

    Science.gov (United States)

    Yong, Ken-Tye; Ding, Hong; Roy, Indrajit; Law, Wing-Cheung; Bergey, Earl J; Maitra, Anirban; Prasad, Paras N

    2009-03-24

    In this paper, we report the successful use of non-cadmium-based quantum dots (QDs) as highly efficient and nontoxic optical probes for imaging live pancreatic cancer cells. Indium phosphide (core)-zinc sulfide (shell), or InP/ZnS, QDs with high quality and bright luminescence were prepared by a hot colloidal synthesis method in nonaqueous media. The surfaces of these QDs were then functionalized with mercaptosuccinic acid to make them highly dispersible in aqueous media. Further bioconjugation with pancreatic cancer specific monoclonal antibodies, such as anticlaudin 4 and antiprostate stem cell antigen (anti-PSCA), to the functionalized InP/ZnS QDs, allowed specific in vitro targeting of pancreatic cancer cell lines (both immortalized and low passage ones). The receptor-mediated delivery of the bioconjugates was further confirmed by the observation of poor in vitro targeting in nonpancreatic cancer based cell lines which are negative for the claudin-4-receptor. These observations suggest the immense potential of InP/ZnS QDs as non-cadmium-based safe and efficient optical imaging nanoprobes in diagnostic imaging, particularly for early detection of cancer.

  2. Pancreatic cancer: Are "liquid biopsies" ready for prime-time?

    Science.gov (United States)

    Lewis, Alexandra R; Valle, Juan W; McNamara, Mairead G

    2016-08-28

    Pancreatic cancer is a disease that carries a poor prognosis. Accurate tissue diagnosis is required. Tumours contain a high content of stromal tissue and therefore biopsies may be inconclusive. Circulating tumour cells (CTCs) have been investigated as a potential "liquid biopsy" in several malignancies and have proven to be of prognostic value in breast, prostate and colorectal cancers. They have been detected in patients with localised and metastatic pancreatic cancer with sensitivities ranging from 38%-100% using a variety of platforms. Circulating tumour DNA (ctDNA) has also been detected in pancreas cancer with a sensitivity ranging from 26%-100% in studies across different platforms and using different genetic markers. However, there is no clear consensus on which platform is the most effective for detection, nor which genetic markers are the most useful to use. Potential roles of liquid biopsies include diagnosis, screening, guiding therapies and prognosis. The presence of CTCs or ctDNA has been shown to be of prognostic value both at diagnosis and after treatment in patients with pancreatic cancer. However, more prospective studies are required before this promising technology is ready for adoption into routine clinical practice.

  3. Dickkopf3 overexpression inhibits pancreatic cancer cell growth in vitro

    Institute of Scientific and Technical Information of China (English)

    Yu-Mei Gu; Yi-Hui Ma; Wu-Gan Zhao; Jie Chen

    2011-01-01

    AIM: To elucidate the role of dickkopf3 (Dkk3) in human pancreatic cancer cell growth.METHODS: Dkk3 mRNA and protein expression in human pancreatic cancer cell lines were detected by real-time reverse transcription polymerase chain reaction (real-time RT-PCR), Western blotting and immunofluorescence. Methylation of the Dkk3 promoter sequence was examined by methylation-specific polymerase chain reaction (MSP) and Dkk3 mRNA expression was determined by real-time RT-PCR after 5-aza-2'-deoxycytidine (5-aza-dC) treatment. The effects of Dkk3 on cancer cell proliferation and in vitro sensitivity to gemcitabine were investigated by CellTiter 96. AQueous One Solution Cell Proliferation Assay (MTS) after transfecting the Dkk3 expression plasmid into human pancreatic cancer cells. The expression of β-catenin, phosphorylated extracellular signal-regulated protein kinases (pERK) and extracellular signal-regulated protein kinases (ERK) was also examined by real-time RT-PCR and Western blotting after upregulating Dkk3 expression in human pancreatic cancer cells.RESULTS: The results show that the expression levels of both Dkk3 mRNA and protein were low in all pancreatic cancer cell lines tested. The Dkk3 promoter sequence was methylated in the MIA PaCa-2 and AsPC-1 cell lines, which showed reduced Dkk3 expression. These two cell lines, which initially had a methylated Dkk3 promoter, showed increased Dkk3 mRNA expression that was dependent upon the dosage and timing of the DNA demethylating agent, 5-aza-dC, treatment (P < 0.05 or P < 0.01). When Dkk3 expression was upregulated following the transfection of a Dkk3 expression plasmid into MIA PaCa-2 cells, the ability of cells to proliferate decreased (P < 0.01), and the expression of β-catenin and pERK was downregulated (P < 0.01). Sensitivity to gemcitabine was enhanced in Dkk3 expression plasmid-transfected cells.CONCLUSION: Our findings, for the first time, implicate Dkk3 as a tumor suppressor in human pancreatic cancer

  4. Assessing Drug Efficacy in a Miniaturized Pancreatic Cancer In Vitro 3D Cell Culture Model.

    Science.gov (United States)

    Shelper, Todd B; Lovitt, Carrie J; Avery, Vicky M

    2016-09-01

    Pancreatic cancer continues to have one of the poorest prognoses among all cancers. The drug discovery efforts for this disease have largely failed, with no significant improvement in survival outcomes for advanced pancreatic cancer patients over the past 20 years. Traditional in vitro cell culture techniques have been used extensively in both basic and early drug discovery; however, these systems offer poor models to assess emerging therapeutics. More predictive cell-based models, which better capture the cellular heterogeneity and complexities of solid pancreatic tumors, are urgently needed not only to improve drug discovery success but also to provide insight into the tumor biology. Pancreatic tumors are characterized by a unique micro-environment that is surrounded by a dense stroma. A complex network of interactions between extracellular matrix (ECM) components and the effects of cell-to-cell contacts may enhance survival pathways within in vivo tumors. This biological and physical complexity is lost in traditional cell monolayer models. To explore the predictive potential of a more complex cellular system, a three-dimensional (3D) micro-tumor assay was evaluated. Efficacy of six current chemotherapeutics was determined against a panel of primary and metastatic pancreatic tumor cell lines in a miniaturized ECM-based 3D cell culture system. Suitability for potential use in high-throughput screening applications was assessed, including ascertaining the effects that miniaturization and automation had on assay robustness. Cellular health was determined by utilizing an indirect population-based metabolic activity assay and a direct imaging-based cell viability assay.

  5. Effects of capsid-modified oncolytic adenoviruses and their combinations with gemcitabine or silica gel on pancreatic cancer.

    Science.gov (United States)

    Kangasniemi, Lotta; Parviainen, Suvi; Pisto, Tommi; Koskinen, Mika; Jokinen, Mika; Kiviluoto, Tuula; Cerullo, Vincenzo; Jalonen, Harry; Koski, Anniina; Kangasniemi, Anna; Kanerva, Anna; Pesonen, Sari; Hemminki, Akseli

    2012-07-01

    Conventional cancer treatments often have little impact on the course of advanced pancreatic cancer. Although cancer gene therapy with adenoviruses is a promising developmental approach, the primary receptor is poorly expressed in pancreatic cancers which might compromise efficacy and thus targeting to other receptors could be beneficial. Extended stealth delivery, combination with standard chemotherapy or circumvention of host antiadenoviral immune response might improve efficacy further. In this work, capsid-modified adenoviruses were studied for transduction of cell lines and clinical normal and tumor tissue samples. The respective oncolytic viruses were tested for oncolytic activity in vitro and in vivo. Survival was studied in a peritoneally disseminated pancreas cancer model, with or without concurrent gemcitabine while silica implants were utilized for extended intraperitoneal virus delivery. Immunocompetent mice and Syrian hamsters were used to study the effect of silica mediated delivery on antiviral immune responses and subsequent in vivo gene delivery. Capsid modifications selectively enhanced gene transfer to malignant pancreatic cancer cell lines and clinical samples. The respective oncolytic viruses resulted in increased cell killing in vitro, which translated into a survival benefit in mice. Early proinfammatory cytokine responses and formation of antiviral neutralizing antibodies was partially avoided with silica implants. The implant also shielded the virus from pre-existing neutralizing antibodies, while increasing the pancreas/liver gene delivery ratio six-fold. In conclusion, capsid modified adenoviruses would be useful for testing in pancreatic cancer trials. Silica implants might increase the safety and efficacy of the approach.

  6. Prognostic Significance of Carbohydrate Antigen 19-9 in Unresectable Locally Advanced Pancreatic Cancer Treated With Dose-Escalated Intensity Modulated Radiation Therapy and Concurrent Full-Dose Gemcitabine: Analysis of a Prospective Phase 1/2 Dose Escalation Study

    Energy Technology Data Exchange (ETDEWEB)

    Vainshtein, Jeffrey M., E-mail: jvainsh@med.umich.edu [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Schipper, Matthew [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Zalupski, Mark M. [Division of Hematology Oncology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan (United States); Lawrence, Theodore S. [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Abrams, Ross [Department of Radiation Oncology, Rush Medical Center, Chicago, Illinois (United States); Francis, Isaac R. [Department of Radiology, University of Michigan, Ann Arbor, Michigan (United States); Khan, Gazala [Division of Hematology Oncology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan (United States); Leslie, William [Division of Hematology Oncology, Department of Internal Medicine, Rush Medical Center, Chicago, Illinois (United States); Ben-Josef, Edgar [Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania (United States)

    2013-05-01

    Purpose: Although established in the postresection setting, the prognostic value of carbohydrate antigen 19-9 (CA19-9) in unresectable locally advanced pancreatic cancer (LAPC) is less clear. We examined the prognostic utility of CA19-9 in patients with unresectable LAPC treated on a prospective trial of intensity modulated radiation therapy (IMRT) dose escalation with concurrent gemcitabine. Methods and Materials: Forty-six patients with unresectable LAPC were treated at the University of Michigan on a phase 1/2 trial of IMRT dose escalation with concurrent gemcitabine. CA19-9 was obtained at baseline and during routine follow-up. Cox models were used to assess the effect of baseline factors on freedom from local progression (FFLP), distant progression (FFDP), progression-free survival (PFS), and overall survival (OS). Stepwise forward regression was used to build multivariate predictive models for each endpoint. Results: Thirty-eight patients were eligible for the present analysis. On univariate analysis, baseline CA19-9 and age predicted OS, CA19-9 at baseline and 3 months predicted PFS, gross tumor volume (GTV) and black race predicted FFLP, and CA19-9 at 3 months predicted FFDP. On stepwise multivariate regression modeling, baseline CA19-9, age, and female sex predicted OS; baseline CA19-9 and female sex predicted both PFS and FFDP; and GTV predicted FFLP. Patients with baseline CA19-9 ≤90 U/mL had improved OS (median 23.0 vs 11.1 months, HR 2.88, P<.01) and PFS (14.4 vs 7.0 months, HR 3.61, P=.001). CA19-9 progression over 90 U/mL was prognostic for both OS (HR 3.65, P=.001) and PFS (HR 3.04, P=.001), and it was a stronger predictor of death than either local progression (HR 1.46, P=.42) or distant progression (HR 3.31, P=.004). Conclusions: In patients with unresectable LAPC undergoing definitive chemoradiation therapy, baseline CA19-9 was independently prognostic even after established prognostic factors were controlled for, whereas CA19-9 progression

  7. Induction Chemotherapy With Gemcitabine, Oxaliplatin, and 5-Fluorouracil/Leucovorin Followed by Concomitant Chemoradiotherapy in Patients With Locally Advanced Pancreatic Cancer: A Taiwan Cooperative Oncology Group Phase II Study

    Energy Technology Data Exchange (ETDEWEB)

    Ch' ang, Hui-Ju [National Institute of Cancer Research, National Health Research Institutes, Miaoli, Taiwan (China); Department of Radiation Oncology, National Cheng Kung University Hospital, Tainan, Taiwan (China); Lin, Yu-Lin [Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan (China); Wang, Hsiu-Po [Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan (China); Chiu, Yen-Feng [Institute of Public Health Sciences, National Health Research Institutes, Miaoli, Taiwan (China); Chang, Ming-Chu [Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan (China); Hsu, Chih-Hung [Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan (China); Tien, Yu-Wen [Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan (China); Chen, Jen-Shi [Department of Internal Medicine, Chang-Gung Memorial Hospital, Chang Gung University, College of Medicine, Tao-Yuan, Taiwan (China); Hsieh, Ruey-Kuen [Department of Internal Medicine, Mackay Memorial Hospital, Taipei, Taiwan (China); Lin, Pin-Wen; Shan, Yan-Shen [Department of Surgery, National Cheng Kung University Hospital, Tainan, Taiwan (China); Cheng, Ann-Lii [Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan (China); Chang, Jang-Yang [National Institute of Cancer Research, National Health Research Institutes, Miaoli, Taiwan (China); Department of Internal Medicine, National Cheng Kung University Hospital, Tainan, Taiwan (China); Whang-Peng, Jacqueline [National Institute of Cancer Research, National Health Research Institutes, Miaoli, Taiwan (China); Cancer Center Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan (China); Hwang, Tsann-Long, E-mail: hwangtl@adm.cgmh.org.tw [Department of Surgery, Chang-Gung Memorial Hospital, Chang Gung University, College of Medicine, Tao-Yuan, Taiwan (China); and others

    2011-12-01

    Purpose: To evaluate the therapeutic efficacy of 3-month triplet induction chemotherapy (ICT) followed by concomitant chemoradiotherapy (CCRT) in patients with locally advanced pancreatic cancer (LAPC). Patients and Methods: Chemonaieve patients with measurable, histologically confirmed LAPC were eligible. The ICT consisted of biweekly gemcitabine (800 mg/m{sup 2}) infusion at a fixed dose rate (10 mg/m{sup 2}/min), followed by 85 mg/m{sup 2} oxaliplatin and 48-h infusion of 5-fluorouracil/leucovorin (3000/150 mg/m{sup 2}) for 6 cycles. Patients without disease progression 4 weeks after ICT would receive weekly 400 mg/m{sup 2} gemcitabine and 5040 cGy radiation in 28 fractions. After CCRT, patients were subjected for surgical intervention and/or maintenance chemotherapy until progression or intolerable toxicity. Results: Between December 2004 and August 2008, 50 patients were enrolled. The best responses after ICT were partial response (PR) in 9, stable disease in 26, and progressive disease or not evaluable in 15. Among the former 35 patients, 2 had disease progression before CCRT, and 3 declined to have CCRT. Of the 30 patients receiving CCRT, an additional 4 and 1 patient(s) achieved PR at the end of CCRT and during maintenance chemotherapy, respectively. On intent-to-treat analysis, the overall best response was PR in 14 patients and stable disease in 21. The overall response rate and disease control rate were 28% (95% confidence interval [CI], 16.2-42.5%) and 70% (95% CI, 44.4-99.2%), respectively. The median time to progression and overall survival of the intent-to-treat population was 9.3 (95% CI, 5.8-12.8) months and 14.5 (95% CI, 11.9-17.1) months, respectively. One- and two-year survival rates were 68% (95% CI, 55.1-80.9%) and 20.6% (95% CI, 8.7-32.5%), respectively. Neutropenia was the most common Grade 3-4 toxicity of both ICT and CCRT, with a frequency of 28% and 26.7%, respectively. Significant sensory neuropathy occurred in 9 patients (18

  8. Pancreatic adenocarcinoma pathology : changing "landscape"

    NARCIS (Netherlands)

    Brosens, Lodewijk A A; Hackeng, Wenzel M; Offerhaus, G Johan; Hruban, Ralph H; Wood, Laura D

    2015-01-01

    Pancreatic cancer is a devastating disease. At time of diagnosis the disease is usually advanced and only a minority of patients are eligible for surgical resection. The overall 5-year survival is 6%. However, survival of patients with early stage pancreatic cancer is significantly better. To improv

  9. Drug/Nutrients Interaction in Neoplastic Patients Requiring Nutritional Support. Practical Advice with Special Focusing on Pancreatic Cancer

    OpenAIRE

    Ilaria Uomo; Adele Savoia

    2008-01-01

    Malnutrition and cachexia are frequent complaints in neoplastic disease [1, 2]. Nutritional support and pain treatment still remain the main treatment option for the majority of patients with cancer, particularly for those affected by pancreatic cancer who very often present an advanced stage of the disease at moment of first diagnosis [3, 4, 5]. Therefore, in their clinical practice, physicians are faced with the need for parenteral or enteral nutrition and with the contemporary requirement ...

  10. 高强度聚焦超声治疗胰腺癌的研究进展%Advances of High-intensity Focused Ultrasound on the Treatment of Pancreatic Cancer

    Institute of Scientific and Technical Information of China (English)

    陈依静(综述); 许青(审校)

    2015-01-01

    High-intensity focused ultrasound( HIFU) is a non-invasive technique used for thermal abla-tion in multiple benign and malignant solid tumors. Pancreatic cancer has a dismal prognosis, and most patients are diagnosed at an inoperable stage. Chemotherapy and radiation therapy is not satisfactory enough. So,there is an urge need for new treatments to improve the situation. Clinical trials suggest that HIFU,as part of the comprehensive treatment for patients with pancreatic cancer,may increase the effective rate,median survival time,1-year survival rate and improve the quality of life.%高强度聚焦超声(HIFU)是一种无创局部热消融技术,适用于多种良恶性实体肿瘤的治疗。胰腺癌起病隐匿,恶性程度高,多数患者确诊时已失去手术机会,且化疗、放疗效果欠佳,故需要新的治疗手段改善现状。临床研究显示,HIFU作为综合治疗手段可能提高胰腺癌患者的治疗有效率、中位生存期及1年生存率,改善患者的生活质量。

  11. Whole genomes redefine the mutational landscape of pancreatic cancer

    Science.gov (United States)

    Waddell, Nicola; Pajic, Marina; Patch, Ann-Marie; Chang, David K.; Kassahn, Karin S.; Bailey, Peter; Johns, Amber L.; Miller, David; Nones, Katia; Quek, Kelly; Quinn, Michael C. J.; Robertson, Alan J.; Fadlullah, Muhammad Z. H.; Bruxner, Tim J. C.; Christ, Angelika N.; Harliwong, Ivon; Idrisoglu, Senel; Manning, Suzanne; Nourse, Craig; Nourbakhsh, Ehsan; Wani, Shivangi; Wilson, Peter J; Markham, Emma; Cloonan, Nicole; Anderson, Matthew J.; Fink, J. Lynn; Holmes, Oliver; Kazakoff, Stephen H.; Leonard, Conrad; Newell, Felicity; Poudel, Barsha; Song, Sarah; Taylor, Darrin; Waddell, Nick; Wood, Scott; Xu, Qinying; Wu, Jianmin; Pinese, Mark; Cowley, Mark J.; Lee, Hong C.; Jones, Marc D.; Nagrial, Adnan M.; Humphris, Jeremy; Chantrill, Lorraine A.; Chin, Venessa; Steinmann, Angela M.; Mawson, Amanda; Humphrey, Emily S.; Colvin, Emily K.; Chou, Angela; Scarlett, Christopher J.; Pinho, Andreia V.; Giry-Laterriere, Marc; Rooman, Ilse; Samra, Jaswinder S.; Kench, James G.; Pettitt, Jessica A.; Merrett, Neil D.; Toon, Christopher; Epari, Krishna; Nguyen, Nam Q.; Barbour, Andrew; Zeps, Nikolajs; Jamieson, Nigel B.; Graham, Janet S.; Niclou, Simone P.; Bjerkvig, Rolf; Grützmann, Robert; Aust, Daniela; Hruban, Ralph H.; Maitra, Anirban; Iacobuzio-Donahue, Christine A.; Wolfgang, Christopher L.; Morgan, Richard A.; Lawlor, Rita T.; Corbo, Vincenzo; Bassi, Claudio; Falconi, Massimo; Zamboni, Giuseppe; Tortora, Giampaolo; Tempero, Margaret A.; Gill, Anthony J.; Eshleman, James R.; Pilarsky, Christian; Scarpa, Aldo; Musgrove, Elizabeth A.; Pearson, John V.; Biankin, Andrew V.; Grimmond, Sean M.

    2015-01-01

    Pancreatic cancer remains one of the most lethal of malignancies and a major health burden. We performed whole-genome sequencing and copy number variation (CNV) analysis of 100 pancreatic ductal adenocarcinomas (PDACs). Chromosomal rearrangements leading to gene disruption were prevalent, affecting genes known to be important in pancreatic cancer (TP53, SMAD4, CDKN2A, ARID1A and ROBO2) and new candidate drivers of pancreatic carcinogenesis (KDM6A and PREX2). Patterns of structural variation (variation in chromosomal structure) classified PDACs into 4 subtypes with potential clinical utility: the subtypes were termed stable, locally rearranged, scattered and unstable. A significant proportion harboured focal amplifications, many of which contained druggable oncogenes (ERBB2, MET, FGFR1, CDK6, PIK3R3 and PIK3CA), but at low individual patient prevalence. Genomic instability co-segregated with inactivation of DNA maintenance genes (BRCA1, BRCA2 or PALB2) and a mutational signature of DNA damage repair deficiency. Of 8 patients who received platinum therapy, 4 of 5 individuals with these measures of defective DNA maintenance responded. PMID:25719666

  12. Establishment of risk model for pancreatic cancer in Chinese Han population

    Institute of Scientific and Technical Information of China (English)

    Xing-Hua Lu; Li Wang; Hui Li; Jia-Ming Qian; Rui-Xue Deng; Lu Zhou

    2006-01-01

    AIM: To investigate risk factors for pancreatic cancer and establish a risk model for Han population.METHODS: This population-based case-control study was carried out from January 2002 to April 2004. One hundred and nineteen pancreatic cancer patients and 238 healthy people completed the questionnaire which was used for risk factor analysis. Logistic regression analysis was used to calculate odds ratio (ORs), 95%confidence intervals (Cis) and β value, which were further used to establish the risk model.RESULTS: According to the study, people who have smoked more than 17 pack-years had a higher risk to develop pancreatic cancer compared to non-smokers or light smokers (not more than 17 pack-years) (OR 1.98;95% CI 1.11-3.49, P=0.017). More importantly, heavy smokers in men had increased risk for developing pancreatic cancer (OR 2.11; 95%CI 1.18-3.78, P=0.012)than women. Heavy alcohol drinkers (>20 cup-years)had increased risk for pancreatic cancer (OR 3.68;95%CI 1.60-8.44). Daily diet with high meat intak was also linked to pancreatic cancer. Moreover, 18.5% of the pancreatic cancer patients had diabetes mellitus compared to the control group of 5.8% (P= 0.0003). Typical symptoms of pancreatic cancer were anorexia, upper abdominal pain, bloating, jaundice and weight loss. Each risk factor was assigned a value to represent its impor tance associated with pancreatic cancer. Subsequently by adding all the points together, a risk scoring model was established with a value higher than 45 as being at risk to develop pancreatic cancer.CONCLUSION: Smoking, drinking, high meat diet and diabetes are major risk factors for pancreatic cancer. A risk model for pancreatic cancer in Chinese Hah population has been established with an 88.9% sensitivity and a 97.6% specificity.

  13. SIRT1 inhibition in pancreatic cancer models: contrasing effects in vitro and in vivo

    NARCIS (Netherlands)

    Oon, Chern Ein; Strell, Carina; Yeong, Keng Yoon; Östman, Arne; Prakash, Jai

    2015-01-01

    Gemcitabine remains the standard treatment for pancreatic cancer, although most patients acquire resistance to the therapy. Up-regulated in pancreatic cancer, SIRT1 is involved in tumorigenesis and drug resistance. However the mechanism through which SIRT1 regulates drug sensitivity in cancer cells

  14. Critical analysis of the potential for the therapeutic targeting of the Sp1 transcription factor in pancreatic cancer

    Directory of Open Access Journals (Sweden)

    Jutooru I

    2014-06-01

    Full Text Available Indira Jutooru,1 Gayathri Chadalapaka,1 Stephen Safe1,21Department of Veterinary Physiology and Pharmacology, Texas A&M University, College Station, TX, USA; 2Institute of Biosciences and Technology, Texas A&M Health Science Center, Houston, TX, USAAbstract: Pancreatic ductal adenocarcinoma (PDAC is a major cause of cancer-related deaths in developed countries and, in 2013, it is estimated that in excess of 45,220 new cases were diagnosed in the United States. PDAC is a highly aggressive disease that invariably evades early diagnosis. The mean survival time for patients with metastatic disease is only 3–6 months, and only 20%–30% of pancreatic cancer patients are alive after 12 months. Because pancreatic cancers are frequently detected at an advanced stage, treatments have provided very limited improvements in tumor regression and overall survival times after diagnosis. 5-Fluorouracil alone or in combination with other drugs has been extensively used for treatment of advanced pancreatic cancer, and gemcitabine has partially replaced 5-fluorouracil as a treatment for pancreatic cancer. Gemcitabine provides increased clinical benefits in terms of response rate; however, future studies need to focus on developing treatment modalities that will improve the survival rate for pancreatic cancer patients. Specificity protein 1 (Sp1 is overexpressed in PDAC patients, and high expression is associated with poor prognosis, lymph node metastasis, and low survival. Knockdown studies have shown that Sp1 plays an important role in cell growth, angiogenesis, inflammation, survival, and metastasis. Sp1 expression is low in normal tissue when compared to tumor tissue, which makes Sp1 a potential target for development of new mechanism-based drugs for treatment of pancreatic cancer. Several drugs such as tolfenamic acid, betulinic acid, and methyl-2-cyano3,12-dioxooleana-1,9(11-dien-28-oate are shown to downregulate Sp1 expression through various pathways

  15. 胰腺癌:靶向治疗的前景%Pancreatic cancer-Outlook:targeted therapy

    Institute of Scientific and Technical Information of China (English)

    Patrick Michl; Thomas M. Gress

    2007-01-01

    Pancreatic cancer is a devastating disease characterized by almost identical incidence and mortality rates. Since this tumour is mostly diagnosed in an advanced stage there is usually no option for a curative surgical resection. In addition,pancreatic cancers known to be resistant to conventional treatment modalities such as chemotherapy and radiotherapy.Therefore, novel strategies for targeting these tumors are urgently needed. The increasing knowledge on the underlying pathogenetic mechanisms has led to the identification of surface receptor molecules that initiate intracellular signalling cascades upon ligand binding, thus leading to tumor progression. Targeting these receptors or their secreted ligands is therefore an attractive new approach for cancer therapy. The epidermal growth factor receptor (EGFR) and the vascular endothelial growth factor receptor (VEGFR) are transmembrane tyrosine kinase receptors which can be targeted by various compounds such as antibodies or small molecule inhibitors. In addition, various molecules targeting proteins secreted by pancreatic cancers such as matrix metalloproteinases (MMP's) or intracellular oncogenic signalling components such as the famesyltransferase have been proposed as potential new approaches for targeted cancer therapy. The use of these agents alone or in combination with conventional therapeutic regimens is currently being evaluated and shows first promising results for pancreatic cancer therapy.

  16. Pancreatitis

    Science.gov (United States)

    ... the hormones insulin and glucagon into the bloodstream. Pancreatitis is inflammation of the pancreas. It happens when digestive enzymes start digesting the pancreas itself. Pancreatitis can be acute or chronic. Either form is ...

  17. Advanced Cancer Detection Center

    Science.gov (United States)

    2000-10-01

    Coeur d’Alene, ID IASLC 9th World Conference on Lung Cancer, Cellular Targeting in the Molecular Diagnosis of Lung Cancer, Tokyo, Japan The...World Conference on Lung Cancer, Cellular Targeting in the Molecular Diagnosis of Lung Cancer, Tokyo, Japan The first International Conference on

  18. ROLE OF RAC-1 DEPENDENT NADPH OXIDASE IN THE GROWTH OF PANCREATIC CANCER

    OpenAIRE

    2010-01-01

    K-ras mutations occur in as high as 95% of patients with pancreatic cancer. K-ras activates Rac1-dependent NADPH oxidase, a key source of superoxide. Superoxide plays an important role in pancreatic cancer cell proliferation and scavenging or decreasing the levels of superoxide inhibits pancreatic cancer cell growth both in vitro and in vivo. DNA microarray analysis and RT-PCR has demonstrated that Rac1 is also upregulated in pancreatic cancer. The aim of this study was to determine if inhibi...

  19. Lipoxygenase and cyclooxygenase metabolism: new insights in treatment and chemoprevention of pancreatic cancer

    Directory of Open Access Journals (Sweden)

    Adrian Thomas E

    2003-01-01

    Full Text Available Abstract The essential fatty acids, linoleic acid and arachidonic acid play an important role in pancreatic cancer development and progression. These fatty acids are metabolized to eicosanoids by cyclooxygenases and lipoxygenases. Abnormal expression and activities of both cyclooxygenases and lipoxygenases have been reported in pancreatic cancer. In this article, we aim to provide a brief summary of (1 our understanding of the roles of these enzymes in pancreatic cancer tumorigenesis and progression; and (2 the potential of using cyclooxygenase and lipoxygenase inhibitors for pancreatic cancer treatment and prevention.

  20. Adipose tissue-derived stem cells promote pancreatic cancer cell proliferation and invasion

    Energy Technology Data Exchange (ETDEWEB)

    Ji, S.Q.; Cao, J. [Department of Liver Surgery I, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai (China); Zhang, Q.Y.; Li, Y.Y. [Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Wenzhou Medical College, Wenzhou (China); Yan, Y.Q. [Department of Liver Surgery I, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai (China); Yu, F.X. [Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Wenzhou Medical College, Wenzhou (China)

    2013-09-27

    To explore the effects of adipose tissue-derived stem cells (ADSCs) on the proliferation and invasion of pancreatic cancer cells in vitro and the possible mechanism involved, ADSCs were cocultured with pancreatic cancer cells, and a cell counting kit (CCK-8) was used to detect the proliferation of pancreatic cancer cells. ELISA was used to determine the concentration of stromal cell-derived factor-1 (SDF-1) in the supernatants. RT-PCR was performed to detect the expression of the chemokine receptor CXCR4 in pancreatic cancer cells and ADSCs. An in vitro invasion assay was used to measure invasion of pancreatic cancer cells. SDF-1 was detected in the supernatants of ADSCs, but not in pancreatic cancer cells. Higher CXCR4 mRNA levels were detected in the pancreatic cancer cell lines compared with ADSCs (109.3±10.7 and 97.6±7.6 vs 18.3±1.7, respectively; P<0.01). In addition, conditioned medium from ADSCs promoted the proliferation and invasion of pancreatic cancer cells, and AMD3100, a CXCR4 antagonist, significantly downregulated these growth-promoting effects. We conclude that ADSCs can promote the proliferation and invasion of pancreatic cancer cells, which may involve the SDF-1/CXCR4 axis.

  1. Erlotinib-Induced Episcleritis in a Patient with Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Armin Shahrokni

    2008-03-01

    Full Text Available Context Erlotinib is a relatively new anilinoquinazoline indicated for treatment of pancreatic cancer in combination with gemcitabine. It is a tyrosine kinase inhibitor that specifically targets epidermal growth factor receptor (EGFR, which is commonly overexpressed and/or mutated in solid tumors. Active competitive inhibition of adenosine triphosphate, inhibits downstream signal transduction of ligand dependent EGFR activation. EGFR kinase inhibitors are less toxic than conventional chemotherapy as they are relatively specific for tumor cells. Common side effects include acneiform (papulopustular rash, diarrhea, edema, pruritus, dry skin and alopecia. Case report This article reports the case of a 55-year-old Caucasian female with recurrent pancreatic cancer who developed episcleritis after seventeen days of treatment with erlotinib. Symptoms completely resolved four weeks after drug discontinuation. Conclusions To our knowledge, erlotinibinduced episcleritis has not been previously described.

  2. Myxoma Virus Sensitizes Cancer Cells to Gemcitabine and Is an Effective Oncolytic Virotherapeutic in Models of Disseminated Pancreatic Cancer

    OpenAIRE

    Wennier, Sonia Tusell; Liu, Jia; Li, Shoudong; Rahman, Masmudur M.; Mona, Mahmoud; McFadden, Grant

    2012-01-01

    Myxoma virus (MYXV) is a novel oncolytic virus that has been shown to replicate in pancreatic cancer cells, but its efficacy in animal models of pancreatic cancer has not been determined. The efficacy of MYXV as monotherapy or in combination with gemcitabine was evaluated in intraperitoneal dissemination (IPD) models of pancreatic cancer. The effects of an intact immune system on the efficacy of MYXV therapy was tested by comparing immunodeficient versus immunocompetent murine models and comb...

  3. Pancreatitis

    Institute of Scientific and Technical Information of China (English)

    1997-01-01

    970359 CT diagnosis of pancreatic carcinoma andchronic pancreatitis. LUAN Baoqing(栾宝庆), et al,Dept Radiol, Beijing Friendship Hosp, Capital Med U-niv, Beijing, 100050. Chin J Radiol 1997; 31(2): 114-118. Objective: To improve the diagnostic accuracy ofpancreatic carcinoma and chronic pancreatitis. Materi-

  4. Recent advances in autoimmune pancreatitis: concept, diagnosis, and pathogenesis.

    Science.gov (United States)

    Okazaki, Kazuichi; Uchida, Kazushige; Fukui, Toshiro

    2008-01-01

    Recent advances support the concept of autoimmune pancreatitis (AIP) as a unique systemic disease, because it shows occasional extrapancreatic lesions such as sclerosing cholangitis, sclerosing sialoadenitis, and retroperitoneal fibrosis, pathological features similar to those of fibrosis, and abundant infiltration of IgG4-positive plasma cells, and it is steroid responsive. Based on these findings, several diagnostic criteria have been proposed. Although AIP is accepted worldwide as a unique clinical entity, its pathogenetic mechanism remains unclear. To clarify its pathogenesis, its genetic background, humoral immunity, candidate target antigens including self-antigens and molecular mimicry by microbes, and cellular immunity including regulatory T cells, the complement system, and experimental models are reviewed. On the basis of this review, we hypothesize that the pathogenesis of AIP involves a biphasic mechanism consisting of "induction" and "progression." In the early stage, the initial response to self-antigens [lactoferrin, carbonic anhydrase (CA)-II, CA-IV, pancreatic secretory trypsin inhibitor, and alpha-fodrin] and molecular mimicry (Helicobacter pylori) are induced by decreased naïve regulatory T cells (Tregs), and T-helper (Th) 1 cells release proinflammatory cytokines [interferon-gamma, interleukin (IL)-1beta, IL-2, and tumor necrosis factor alpha]. In the chronic stage, progression is supported by increased memory Tregs and Th2 immune responses. The classical complement system pathway may be activated by the IgG1 immune complex. As Tregs seem to play an important role in progression as well as in induction of the disease, further studies are necessary to clarify the pathogenesis of AIP.

  5. Feasibility of alternating induction and maintenance chemotherapy in pancreatic cancer

    OpenAIRE

    Hann, Alexander; Bohle, Wolfram; Egger, Jan; Zoller, Wolfram

    2017-01-01

    Chemotherapy regimens for pancreatic ductal adenocarcinoma (PDAC) have changed since the introduction of FOLFIRINOX. Due to toxicity, dosage and number of applied cycles are limited. In analogy to chemotherapy strategies in colon cancer we used a scheme of induction, maintenance and re-induction therapy in PDAC to alleviate such toxicities and increase the number of applied cycles. Here we report first experiences with this approach. Data of all patients who received FOLFIRINOX for metastatic...

  6. Adipocytes and Neutrophils Give a Helping Hand to Pancreatic Cancers.

    Science.gov (United States)

    Bronte, Vincenzo; Tortora, Giampaolo

    2016-08-01

    Obesity-induced inflammation can build up a confined microenvironment in pancreatic adenocarcinoma that is associated with increased desmoplasia, neutrophil recruitment, reduced delivery of chemotherapeutic drugs, and immune evasion. Targeting molecular pathways empowering this circuit might represent a necessary measure to reach clinical efficacy for combination therapies in patients with excess body weight. Cancer Discov; 6(8); 821-3. ©2016 AACR.See related article by Incio et al., p. 852.

  7. Molecular analysis of precursor lesions in familial pancreatic cancer.

    Directory of Open Access Journals (Sweden)

    Tatjana Crnogorac-Jurcevic

    Full Text Available BACKGROUND: With less than a 5% survival rate pancreatic adenocarcinoma (PDAC is almost uniformly lethal. In order to make a significant impact on survival of patients with this malignancy, it is necessary to diagnose the disease early, when curative surgery is still possible. Detailed knowledge of the natural history of the disease and molecular events leading to its progression is therefore critical. METHODS AND FINDINGS: We have analysed the precursor lesions, PanINs, from prophylactic pancreatectomy specimens of patients from four different kindreds with high risk of familial pancreatic cancer who were treated for histologically proven PanIN-2/3. Thus, the material was procured before pancreatic cancer has developed, rather than from PanINs in a tissue field that already contains cancer. Genome-wide transcriptional profiling using such unique specimens was performed. Bulk frozen sections displaying the most extensive but not microdissected PanIN-2/3 lesions were used in order to obtain the holistic view of both the precursor lesions and their microenvironment. A panel of 76 commonly dysregulated genes that underlie neoplastic progression from normal pancreas to PanINs and PDAC were identified. In addition to shared genes some differences between the PanINs of individual families as well as between the PanINs and PDACs were also seen. This was particularly pronounced in the stromal and immune responses. CONCLUSIONS: Our comprehensive analysis of precursor lesions without the invasive component provides the definitive molecular proof that PanIN lesions beget cancer from a molecular standpoint. We demonstrate the need for accumulation of transcriptomic changes during the progression of PanIN to PDAC, both in the epithelium and in the surrounding stroma. An identified 76-gene signature of PDAC progression presents a rich candidate pool for the development of early diagnostic and/or surveillance markers as well as potential novel preventive

  8. New Strategies in Pancreatic Cancer: Emerging Epidemiological and Therapeutic Concepts

    OpenAIRE

    Li, Donghui; Abbruzzese, James L.

    2010-01-01

    Pancreatic cancer (PC) is a highly lethal disease with complex etiology involving both environmental and genetic factors. While cigarette smoking is known to explain 25% of cases, data from recent studies suggest that obesity and long-term type II diabetes are two major modifiable risk factors for PC. Furthermore, obesity and diabetes appear to affect the clinical outcome of patients with PC. Understanding the mechanistic effects of obesity and diabetes on the pancreas may identify new strate...

  9. Occupational exposures and pancreatic cancer: a meta-analysis

    OpenAIRE

    Ojajarvi, I; Partanen, T.; Ahlbom, A; Boffetta, P; Hakulinen, T; Jourenkova, N.; Kauppinen, T; Kogevinas, M.; Porta, M; Vainio, H.; E. Weiderpass; Wesseling, C.

    2000-01-01

    OBJECTIVES—Consolidation of epidemiological data on pancreatic cancer and worksite exposures.
METHODS—Publications during 1969-98 were surveyed. Studies without verified exposures were excluded. Meta-analyses were conducted on data from 92 studies covering 161 populations, with results for 23 agents or groups of agents. With a standard format, five epidemiologists extracted risk estimates and variables of the structure and quality of each study. The extracted data were centrally checked. Rand...

  10. Comprehensive Evaluation of Altered Systemic Metabolism and Pancreatic Cancer Risk

    Science.gov (United States)

    2015-10-01

    Major Task 4: Generate and analyze metabolites related to branched chain amino acid ( BCAA ) metabolism. 3 Major Task 4 included analyses of...branched chain amino acid ( BCAA ) catabolic products (months 10-15), quality control of data (months 16-17), and analysis of BCAA catabolic products with...pancreatic cancer development (months 18-23). We have completed measurement of BCAA catabolic products in our plasma samples and have begun the

  11. Chinese Herbal Medicines as an Adjunctive Therapy for Unresectable Pancreatic Cancer: A Systematic Review and Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Bin Li

    2015-01-01

    Full Text Available Pancreatic cancer is a common malignancy with a high mortality. Most patients present clinically with advanced pancreatic cancer. Moreover, the effect of radiotherapy or chemotherapy is limited. Complementary and alternative medicines represent exciting adjunctive therapies. In this study, we ascertained the beneficial and adverse effects of Chinese herbal medicine (CHM in combination with conventional therapy for inoperable pancreatic cancer by using meta-analysis methods for controlled clinical trials. We extracted data for studies searched from six electronic databases that were searched and also assessed the methodological quality of the included studies. We evaluated the following outcome measures: 6-month and 1-year survival rate, objective response rate, disease control rate, quality of life, and adverse effects. The final analysis showed CHM is a promising strategy as an adjunctive therapy to treat advanced or inoperable pancreatic cancer and that CHM in combination with conventional therapy is a promising strategy for resistant disease. However, convincing evidence must be obtained and confirmed by high-quality trials in future studies.

  12. Flavonoid and lignan intake and pancreatic cancer risk in the European prospective investigation into cancer and nutrition cohort

    NARCIS (Netherlands)

    Molina-Montes, Esther; Sánchez, María José; Zamora-Ros, Raul; Bueno-de-Mesquita, H. Bas; Wark, Petra A.; Obon-Santacana, Mireia; Kühn, Tilman; Katzke, Verena; Travis, Ruth C.; Ye, Weimin; Sund, Malin; Naccarati, Alessio; Mattiello, Amalia; Krogh, Vittorio; Martorana, Caterina; Masala, Giovanna; Amiano, Pilar; Huerta, José María; Barricarte, Aurelio; Quirós, José Ramón; Weiderpass, Elisabete; Angell Åsli, Lene; Skeie, Guri; Ericson, Ulrika; Sonestedt, Emily; Peeters, Petra H.; Romieu, Isabelle; Scalbert, Augustin; Overvad, Kim; Clemens, Matthias; Boeing, Heiner; Trichopoulou, Antonia; Peppa, Eleni; Vidalis, Pavlos; Khaw, Kay Tee; Wareham, Nick; Olsen, Anja; Tjønneland, Anne; Boutroun-Rualt, Marie Christine; Clavel-Chapelon, Françoise; Cross, Amanda J.; Lu, Yunxia; Riboli, Elio; Duell, Eric J.

    2016-01-01

    Despite the potential cancer preventive effects of flavonoids and lignans, their ability to reduce pancreatic cancer risk has not been demonstrated in epidemiological studies. Our aim was to examine the association between dietary intakes of flavonoids and lignans and pancreatic cancer risk in the E

  13. Pathway analysis of genome-wide association study data highlights pancreatic development genes as susceptibility factors for pancreatic cancer

    Science.gov (United States)

    Duell, Eric J.; Yu, Kai; Risch, Harvey A.; Olson, Sara H.; Kooperberg, Charles; Wolpin, Brian M.; Jiao, Li; Dong, Xiaoqun; Wheeler, Bill; Arslan, Alan A.; Bueno-de-Mesquita, H. Bas; Fuchs, Charles S.; Gallinger, Steven; Gross, Myron; Hartge, Patricia; Hoover, Robert N.; Holly, Elizabeth A.; Jacobs, Eric J.; Klein, Alison P.; LaCroix, Andrea; Mandelson, Margaret T.; Petersen, Gloria; Zheng, Wei; Agalliu, Ilir; Albanes, Demetrius; Boutron-Ruault, Marie-Christine; Bracci, Paige M.; Buring, Julie E.; Canzian, Federico; Chang, Kenneth; Chanock, Stephen J.; Cotterchio, Michelle; Gaziano, J.Michael; Giovannucci, Edward L.; Goggins, Michael; Hallmans, Göran; Hankinson, Susan E.; Hoffman Bolton, Judith A.; Hunter, David J.; Hutchinson, Amy; Jacobs, Kevin B.; Jenab, Mazda; Khaw, Kay-Tee; Kraft, Peter; Krogh, Vittorio; Kurtz, Robert C.; McWilliams, Robert R.; Mendelsohn, Julie B.; Patel, Alpa V.; Rabe, Kari G.; Riboli, Elio; Shu, Xiao-Ou; Tjønneland, Anne; Tobias, Geoffrey S.; Trichopoulos, Dimitrios; Virtamo, Jarmo; Visvanathan, Kala; Watters, Joanne; Yu, Herbert; Zeleniuch-Jacquotte, Anne; Stolzenberg-Solomon, Rachael Z.

    2012-01-01

    Four loci have been associated with pancreatic cancer through genome-wide association studies (GWAS). Pathway-based analysis of GWAS data is a complementary approach to identify groups of genes or biological pathways enriched with disease-associated single-nucleotide polymorphisms (SNPs) whose individual effect sizes may be too small to be detected by standard single-locus methods. We used the adaptive rank truncated product method in a pathway-based analysis of GWAS data from 3851 pancreatic cancer cases and 3934 control participants pooled from 12 cohort studies and 8 case–control studies (PanScan). We compiled 23 biological pathways hypothesized to be relevant to pancreatic cancer and observed a nominal association between pancreatic cancer and five pathways (P < 0.05), i.e. pancreatic development, Helicobacter pylori lacto/neolacto, hedgehog, Th1/Th2 immune response and apoptosis (P = 2.0 × 10−6, 1.6 × 10−5, 0.0019, 0.019 and 0.023, respectively). After excluding previously identified genes from the original GWAS in three pathways (NR5A2, ABO and SHH), the pancreatic development pathway remained significant (P = 8.3 × 10−5), whereas the others did not. The most significant genes (P < 0.01) in the five pathways were NR5A2, HNF1A, HNF4G and PDX1 for pancreatic development; ABO for H. pylori lacto/neolacto; SHH for hedgehog; TGFBR2 and CCL18 for Th1/Th2 immune response and MAPK8 and BCL2L11 for apoptosis. Our results provide a link between inherited variation in genes important for pancreatic development and cancer and show that pathway-based approaches to analysis of GWAS data can yield important insights into the collective role of genetic risk variants in cancer. PMID:22523087

  14. Gemcitabine-based therapy for pancreatic cancer using the squalenoyl nucleoside monophosphate nanoassemblies.

    Science.gov (United States)

    Maksimenko, Andrei; Caron, Joachim; Mougin, Julie; Desmaële, Didier; Couvreur, Patrick

    2015-03-30

    Gemcitabine is currently the most effective agent against advanced pancreatic cancer. However, the major therapeutic hurdles using gemcitabine include rapid inactivation by blood deaminases and fast development of cell chemoresistance, induced by down-regulation of deoxycytidine kinase or nucleoside transporters. To overcome the above drawbacks we designed recently a novel nanomedicine strategy based on squalenoyl prodrug of 5'-monophosphate gemcitabine (SQdFdC-MP). This amphiphilic conjugate self-organized in water into unilamellar vesicles with a mean diameter of 100 nm. In this study the antitumor efficacy of SQdFdC-MP nanoassemblies (NAs) on chemoresistant and chemosensitive pancreatic adenocarcinoma models have been investigated. Cell viability assays showed that SQdFdC-MP NAs displayed higher antiproliferative and cytotoxic effects, particularly in chemoresistant pancreatic tumor cells. In in vivo studies, SQdFdC-MP NAs decreased significantly the growth (∼70%) of human MiaPaCa2 xenografts, also preventing tumor cell invasion, whereas native dFdC did not display any anticancer activity when tumor growth inhibition was only 35% with SQdFdC NAs. These results correlated with a reduction of Ki-67 antigen and the induction of apoptosis mediated by caspase-3 activation in tumor cells. These findings demonstrated the feasibility of utilizing SQdFdC-MP NAs to make tumor cells more sensitive to gemcitabine and thus providing an efficient new therapeutic alternative for pancreatic adenocarcinoma.

  15. Honokiol arrests cell cycle, induces apoptosis, and potentiates the cytotoxic effect of gemcitabine in human pancreatic cancer cells.

    Directory of Open Access Journals (Sweden)

    Sumit Arora

    Full Text Available Survival rates for patients with pancreatic cancer are extremely poor due to its asymptomatic progression to advanced and metastatic stage for which current therapies remain largely ineffective. Therefore, novel therapeutic agents and treatment approaches are desired to improve the clinical outcome. In this study, we determined the effects of honokiol, a biologically active constituent of oriental medicinal herb Magnolia officinalis/grandiflora, on two pancreatic cancer cell lines, MiaPaCa and Panc1, alone and in combination with the standard chemotherapeutic drug, gemcitabine. Honokiol exerted growth inhibitory effects on both the pancreatic cancer cell lines by causing cell cycle arrest at G₁ phase and induction of apoptosis. At the molecular level, honokiol markedly decreased the expression of cyclins (D1 and E and cyclin-dependent kinases (Cdk2 and Cdk4, and caused an increase in Cdk inhibitors, p21 and p27. Furthermore, honokiol treatment led to augmentation of Bax/Bcl-2 and Bax/Bcl-xL ratios to favor apoptosis in pancreatic cancer cells. These changes were accompanied by enhanced cytoplasmic accumulation of NF-κB with a concomitant decrease in nuclear fraction and reduced transcriptional activity of NF-κB responsive promoter. This was associated with decreased phosphorylation of inhibitor of kappa B alpha (IκB-α causing its stabilization and thus increased cellular levels. Importantly, honokiol also potentiated the cytotoxic effects of gemcitabine, in part, by restricting the gemcitabine-induced nuclear accumulation of NF-κB in the treated pancreatic cancer cell lines. Altogether, these findings demonstrate, for the first time, the growth inhibitory effects of honokiol in pancreatic cancer and indicate its potential usefulness as a novel natural agent in prevention and therapy.

  16. Hepatic artery pseudoaneurysm after surgical treatment for pancreatic cancer: Minimally invasive angiographic techniques as the preferred treatment

    Directory of Open Access Journals (Sweden)

    Sucandy Iswanto

    2014-01-01

    Full Text Available Background: Delayed intra-abdominal bleeding related to hepatic artery pseudoaneurysm is a potentially lethal complication after pancreaticoduodenectomy for pancreatic cancer. Locally advanced tumors, which result in vessel erosion or extensive operative skeletonization, may contribute to weakness of the arterial wall. Reoperation is often technically difficult with high rate of mortality; therefore, alternative less invasive options are ideal. Aims: The study was to present an alternative endovascular treatment of a large hepatic artery pseudoaneurysm after pancreatic resection for locally advanced multicystic adenocarcinoma. Materials and Methods: Transcatheteric mesenteric angiography with deployment of detachable coils in the pseudoaneurysm sac was utilized to manage the hepatic artery pseudoaneurysm. Results: Completion angiography confirmed cessation of contrast enhancement in the pseudoaneurysm sac with preservation of normal antegrade hepatic artery flow. Conclusion: Minimally invasive angiographic technique is the preferred treatment for hepatic artery pseudoaneurysm after pancreatic resections.

  17. Role of endoscopic ultrasound in the diagnosis of pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    Juana; Gonzalo-Marin; Juan; Jose; Vila; Manuel; Perez-Miranda

    2014-01-01

    Endoscopic ultrasonography(EUS) with or without fine needle aspiration has become the main technique for evaluating pancreatobiliary disorders and has proved to have a higher diagnostic yield than positron emission tomography, computed tomography(CT) and transabdominal ultrasound for recognising early pancreatic tumors. As a diagnostic modality for pancreatic cancer, EUS has proved rates higher than 90%, especially for lesions less than 2-3 cm in size in which it reaches a sensitivity rate of 99% vs 55% for CT. Besides, EUS has a very high negative predictive value and thus EUS can reliably exclude pancreatic cancer. The complication rate of EUS is as low as 1.1%-3.0%. New technical developments such as elastography and the use of contrast agents have recently been applied to EUS, improving its diagnostic capability. EUS has been found to be superior to the recent multidetector CT for T stagingwith less risk of overstaying in comparison to both CT and magnetic resonance imaging, so that patients are not being ruled out of a potentially beneficial resection. The accuracy for N staging with EUS is 64%-82%. In unresectable cancers, EUS also plays a therapeutic role by means of treating oncological pain through celiac plexus block, biliary drainage in obstructive jaundice in patients where endoscopic retrograde cholangiopancreatography is not affordable and aiding radiotherapy and chemotherapy.

  18. Pancreatic Cancer: What the Oncologist Can Offer for Palliation